Close
4
USFDA-Insert
X

Overview of Hydrocortisone (Cortisol)

Client Email Product
4p6x
PharmaCompass
4p6x
Also known as: Cortisol, 50-23-7, Acticort, Cetacort, Cortef, 17-hydroxycorticosterone
Molecular Formula
C21H30O5
Molecular Weight
362.466  g/mol
InChI Key
JYGXADMDTFJGBT-VWUMJDOOSA-N
FDA UNII
WI4X0X7BPJ

The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
Hydrocortisone is a Corticosteroid. The mechanism of action of hydrocortisone is as a Corticosteroid Hormone Receptor Agonist.
1 2D Structure

4p6x

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
2.1.2 InChI
InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1
2.1.3 InChI Key
JYGXADMDTFJGBT-VWUMJDOOSA-N
2.1.4 Canonical SMILES
CC12CCC(=O)C=C1CCC3C2C(CC4(C3CCC4(C(=O)CO)O)C)O
2.1.5 Isomeric SMILES
C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)CO)O)C)O
2.2 Other Identifiers
2.2.1 UNII
WI4X0X7BPJ
2.3 Synonyms
2.3.1 Depositor-Supplied Synonyms

1. Cortisol

2. 50-23-7

3. Acticort

4. Cetacort

5. Cortef

6. 17-hydroxycorticosterone

7. Hydrocortisyl

8. Dermacort

9. Hydrasson

10. Cobadex

11. Cortril

12. Hycort

13. Hytone

14. Signef

15. Dihydrocostisone

16. Optef

17. Kendall's Compound F

18. Cortenema

19. Corticreme

20. Cortiment

21. Cortispray

22. Cortonema

23. Dermolate

24. Efcortelan

25. Ficortril

26. Hycortole

27. Hydrocortone

28. Permicort

29. Proctocort

30. Tarcortin

31. Traumaide

32. Alacort

33. Cleiton

34. Cortanal

35. Cortifan

36. Efcorbin

37. Eldecort

38. Genacort

39. Hycortol

40. Hydrocorticosterone

41. Hydroxycortisone

42. Hytone Lotion

43. Hidro-colisona

44. Hydro-adreson

45. Reichstein's Substance M

46. Scheroson F

47. Incortin-h

48. Cort-dome

49. Domolene-hc

50. Epiderm H

51. Esiderm H

52. Otosone-f

53. Polcort H

54. Heb-cort

55. Cortolotion

56. Cortoxide

57. Cremesone

58. Delacort

59. Dermocortal

60. Eldercort

61. Maintasone

62. Mildison

63. Penecort

64. Anflam

65. Dioderm

66. Epicort

67. Rectoid

68. H-cort

69. Hydro-colisona

70. Cortisol Alcohol

71. Ala-scalp

72. Incortin-hydrogen

73. Texacort Lotion 25

74. Aeroseb-hc

75. Anti-inflammatory Hormone

76. Barseb Hc

77. Hydrocortisone Alcohol

78. Komed Hc

79. Nutracort

80. Synacort

81. Texacort

82. Timocort

83. Evacort

84. Hydrocortisone Base

85. Lacticare-hc

86. Ala-cort

87. Algicirtis

88. Cortisolonum

89. Dermaspray

90. Hidrocortisona

91. Hydrocortisone Free Alcohol

92. Hydrocortisonum

93. Kyypakkaus

94. Stiefcorcil

95. Amberin

96. Aquacort

97. Colocort

98. Cortesal

99. Cutisol

100. Flexicort

101. Glycort

102. Hidalone

103. Hytisone

104. Lactisona

105. Lubricort

106. Meusicort

107. Milliderm

108. Sanatison

109. Schericur

110. Sigmacort

111. Uniderm

112. Dermil

113. 11beta-hydroxycortisone

114. Foille Insetti

115. Gyno-cortisone

116. Balneol-hc

117. Basan-corti

118. Clear Aid

119. Cremicort-h

120. Dome-cort

121. Stie-cort

122. Transderma H

123. Beta-hc

124. Remederm Hc

125. Aquanil Hc

126. Cortisporin Otico

127. Derm-aid

128. Heb Cort

129. Neosporin-h Ear

130. Nogenic Hc

131. Scalpicin Capilar

132. Systral Hydrocort

133. Hi-cor

134. Prevex Hc

135. Idrocortisone [dcit]

136. 17alpha-hydroxycorticosterone

137. Alphaderm

138. Cortisporin

139. Efcortelin

140. Fiocortril

141. Hydracort

142. Medicort

143. Zenoxone

144. Drotic

145. Otocort

146. Vytone

147. Nystaform-hc

148. Compound F (kendall)

149. Aeroseb Hc

150. Caldecort Spray

151. Anusol Hc

152. Hydrocortisonum [inn-latin]

153. Genacort (lotion)

154. Hidrocortisona [inn-spanish]

155. Pediotic Suspension

156. Vosol Hc

157. Epicortisol

158. Hydrocortal

159. Idrocortisone

160. Anucort

161. Cortifair

162. Hydroskin

163. Plenadren

164. Protocort

165. 11beta-hydrocortisone

166. Ef Corlin

167. Proctozone Hc

168. Compound F

169. Lacticare Hc

170. Scalp-cort

171. 11-beta-hydrocortisone

172. Rectasol-hc

173. Anucort-hc

174. 11-beta-hydroxycortisone

175. Hydro-rx

176. 11beta,17alpha,21-trihydroxy-4-pregnene-3,20-dione

177. Hc (hydrocortisone)

178. Preparation H Hydrocortisone Cream

179. Proctofoam

180. 11beta,17,21-trihydroxypregn-4-ene-3,20-dione

181. Nsc 10483

182. Chronocort

183. Corhydron

184. Prepcort

185. Duocort

186. Hydrocortisone (cortisol)

187. Unii-wi4x0x7bpj

188. Hydrocortisone In Absorbase

189. Neo-cortef

190. Hc #1

191. Hc #4

192. [3h]cortisol

193. Hc

194. Acticort (tn)

195. Colocort (tn)

196. Otalgine

197. Hysone

198. Cortef (tn)

199. Hytone (tn)

200. Ccris 5854

201. Component Of Otalgine

202. Anusol Hc (tn)

203. Hydrocortisone [inn:ban:jan]

204. 4-pregnene-11beta,17alpha,21-triol-3,20-dione

205. Component Of Lubricort

206. Chebi:17650

207. Cor-oticin

208. Hsdb 3339

209. Nsc10483

210. 11.beta.-hydrocortisone

211. Einecs 200-020-1

212. Wi4x0x7bpj

213. 11.beta.-hydroxycortisone

214. Component Of Neo-cort-dome

215. Acetasol Hc

216. Hydrocort

217. Orlex Hc

218. Terra-cortril

219. Ai3-25006

220. Mls000069609

221. (11beta)-11,17,21-trihydroxypregn-4-ene-3,20-dione

222. (8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one

223. 17.alpha.-hydroxycorticosterone

224. Neo-cort-dome

225. Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11.beta.)-

226. Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-

227. Jygxadmdtfjgbt-vwumjdoosa-n

228. Acetic Acid W/ Hydrocortisone

229. Mfcd00011654

230. Nsc-10483

231. Otic-neo-cort-dome

232. 11beta,17,21-trihydroxyprogesterone

233. Pregn-4-ene-3,20-dione, 11beta,17,21-trihydroxy-

234. Smr000059022

235. Dsstox_cid_714

236. Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11-beta)-

237. Hydrocortisone And Acetic Acid

238. H 4001

239. Calmurid Hc

240. Dsstox_rid_75753

241. 4-pregnen-11beta,17alpha,21-triol-3,20-dione

242. Dsstox_gsid_20714

243. 11beta,17alpha,21-trihydroxypregn-4-ene-3,20-dione

244. 11.beta.,17.alpha.,21-trihydroxypregn-4-ene-3,20-dione

245. Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11b)-

246. Prestwick_265

247. Proctosol-hc

248. (1s,10s,11s,15s,17s,2r,14r)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyl Tetracyclo[8.7.0.0<2,7>.0<11,15>]heptadec-6-en-5-one

249. (1s,2r,10s,11s,14r,15s,17s)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one

250. (8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3h-cyclopenta[a]phenanthren-3-one

251. (8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3(2h)-one

252. Smr000653523

253. (11alpha,14beta)-11,17,21-trihydroxypregn-4-ene-3,20-dione

254. Anusolhc

255. 3h-cortisol

256. 11beta-cortisol

257. Cas-50-23-7

258. Plenadren (tn)

259. Ncgc00022848-06

260. Kendalls Compound F

261. Hydrocortisone [usp:inn:ban:jan]

262. Drotic (salt/mix)

263. Otocort (salt/mix)

264. Hydrocortisone Solution

265. Otalgine (salt/mix)

266. Hydrocortisone, 98%

267. 17-hydrocorticosterone

268. Alphaderm (salt/mix)

269. Hydrocortisone, Topical

270. Otobiotic (salt/mix)

271. Reichsteins Substance M

272. 4p6x

273. Cort-quin (salt/mix)

274. Cortisol, Hydrocortisone

275. Cortisporin (salt/mix)

276. Vosol Hc (salt/mix)

277. Opera_id_1292

278. Prestwick0_000447

279. Prestwick1_000447

280. Prestwick2_000447

281. Prestwick3_000447

282. D0kr5b

283. Epitope Id:174851

284. Upcmld-dp133

285. Ec 200-020-1

286. Ac1l1l2b

287. Schembl4148

288. Hydrocortisone, 98% 1g

289. Hydrocortisone-water Soluble

290. Neo-cort-dome (salt/mix)

291. Lopac0_000594

292. Bspbio_000494

293. Mls001148103

294. Mls002207135

295. Mls002222189

296. Mls002548868

297. Bio-0648

298. Spbio_002433

299. Bpbio1_000544

300. Chembl389621

301. Gtpl2868

302. Pediotic Suspension (salt/mix)

303. Dtxsid7020714

304. Upcmld-dp133:001

305. Bdbm13775

306. Ctk8f3227

307. Otic-neo-cort-dome (salt/mix)

308. 2v95

309. Hydrocortisone (jp15/usp/inn)

310. Hydrocortisone (jp17/usp/inn)

311. Molport-001-794-637

312. Hms1569i16

313. Hms2090m04

314. Hms2096i16

315. Hms2230b18

316. Hms2235f17

317. Hms3259c05

318. Hms3261h10

319. Hydrocortisone, >=98% (hplc)

320. Vioform-hydrocortisone (salt/mix)

321. Hy-n0583

322. Tox21_110883

323. Tox21_200815

324. Tox21_500594

325. Lmst02030001

326. S1696

327. Sbb012589

328. Zinc13540519

329. Akos001582651

330. Tox21_110883_1

331. Ccg-204683

332. Cs-2226

333. Cyclodextrin-encapsulated Hydrocortisone

334. Db00741

335. Lp00594

336. Ls-7439

337. Mcule-8953627920

338. Nc00456

339. 11.beta.,17,21-trihydroxyprogesterone

340. Smp1_000156

341. Ncgc00022848-07

342. Ncgc00022848-09

343. Ncgc00022848-10

344. Ncgc00022848-11

345. Ncgc00022848-12

346. Ncgc00022848-13

347. Ncgc00022848-14

348. Ncgc00022848-15

349. Ncgc00022848-17

350. Ncgc00258369-01

351. Ncgc00261279-01

352. Ac-12902

353. Aj-64104

354. Ak130455

355. An-24370

356. As-11651

357. Bp-20390

358. Cpd000653523

359. Dr001936

360. Nci60_000118

361. Pl057585

362. Sam002264617

363. Sc-18577

364. St069286

365. Ab1009452

366. B1951

367. Eu-0100594

368. 50h237

369. 6861-ep2269977a2

370. 6861-ep2270008a1

371. 6861-ep2277565a2

372. 6861-ep2277566a2

373. 6861-ep2277567a1

374. 6861-ep2277568a2

375. 6861-ep2277569a2

376. 6861-ep2277570a2

377. 6861-ep2292227a2

378. 6861-ep2292280a1

379. 6861-ep2292615a1

380. 6861-ep2292617a1

381. 6861-ep2295409a1

382. 6861-ep2298778a1

383. 6861-ep2305679a1

384. 6861-ep2308562a2

385. 6861-ep2314590a1

386. 6861-ep2371811a2

387. 7062-ep2269977a2

388. 7062-ep2292228a1

389. 7062-ep2295411a1

390. 7062-ep2298747a1

391. 7062-ep2301931a1

392. 7062-ep2308851a1

393. 7062-ep2308880a1

394. 7062-ep2311811a1

395. 7062-ep2314585a1

396. C00735

397. D00088

398. J10114

399. U 1851

400. 92372-ep2280008a2

401. 92372-ep2289483a1

402. 92372-ep2305257a1

403. Hydrocortisone, Meets Usp Testing Specifications

404. Pregn-4-ene-3, 11.beta.,17,21-trihydroxy-

405. 11?,17?,21-trihydroxypregn-4-ene-3,20-dione

406. Hydrocortisone, Vetranal(tm), Analytical Standard

407. Q-201211

408. 11.beta.,17,21-trihydroxypregn-4-ene-3,20-dione

409. Brd-k93568044-001-03-1

410. Hydrocortisone, Bioreagent, Suitable For Cell Culture

411. 4-pregnen-11.beta.,17.alpha.,21-triol-3,20-dione

412. 4-pregnene-11.beta.,17.alpha.,21-triol-3,20-dione

413. Pregn-4-ene-3,20-dione, 11.beta.,17,21-trihydroxy-

414. Z2786051549

415. (11beta)-11,17,21-trihydroxy-pregn-4-ene-3,20-dione

416. 11.beta.,17.alpha.,21-trihydroxy-4-pregnene-3,20-dione

417. B48448a1-24ba-47ca-8d9e-43e5bc949386

418. Pregn-4-ene-3, 11,17,21-trihydroxy-, (11.beta.)-

419. 11,17,21-trihydroxypregn-4-ene-3,20-dione, (11.beta.)-

420. Hydrocortisone, European Pharmacopoeia (ep) Reference Standard

421. Hydrocortisone, United States Pharmacopeia (usp) Reference Standard

422. Hydrocortisone-water Soluble, Bioreagent, Suitable For Cell Culture

423. Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11 Beta)-

424. (8xi,9xi,11beta,14xi)-11,17,21-trihydroxypregn-4-ene-3,20-dione

425. Hydrocortisone, Gamma-irradiated, Powder, Bioxtra, Suitable For Cell Culture

426. 4-(6-chloro-4-oxoquinazolin-3(4h)-yl)-n-(3-methoxyphenyl)piperidine-1-carboxamide

427. Cortisol Solution, 1.0 Mg/ml In Methanol, Ampule Of 1 Ml, Certified Reference Material

428. Hydrocortisone For Peak Identification, European Pharmacopoeia (ep) Reference Standard

429. Hydrocortisone Solution, 50 Mum, Sterile-filtered, Bioxtra, Suitable For Cell Culture

430. Hydrocortisone, Pharmaceutical Secondary Standard; Certified Reference Material

431. (1s,2r,10s,11s,14r,15s,17s)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0(2),.0(1)(1),(1)]heptadec-6-en-5-one

432. (1s,2r,10s,11s,14r,15s,17s)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0(2),?.0(1)(1),(1)?]heptadec-6-en-5-one

433. 1050676-88-4

434. 11

435. A,17

436. A,21-trihydroxypregn-4-ene-3,20-dione; 17-hydroxycorticosterone; 4-pregnene-11

437. A,17

438. A,21-triol-3,20-dione; Cortisol; Kendall Inverted Exclamation Mark S Compound F; Reichstein Inverted Exclamation Mark S Substance M

439. 8056-08-4

440. 80562-38-5

441. 8063-42-1

2.4 Create Date
2004-09-16
3 Chemical and Physical Properties
Molecular Weight 362.466 g/mol
Molecular Formula C21H30O5
XLogP31.6
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count5
Rotatable Bond Count2
Exact Mass362.209 g/mol
Monoisotopic Mass362.209 g/mol
Topological Polar Surface Area94.8 A^2
Heavy Atom Count26
Formal Charge0
Complexity684
Isotope Atom Count0
Defined Atom Stereocenter Count7
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 22  
Drug NameALA-CORT
Active IngredientHYDROCORTISONE
CompanyCROWN LABS (Application Number: A080706)

2 of 22  
Drug NameALA-SCALP
Active IngredientHYDROCORTISONE
CompanyCROWN LABS (Application Number: A083231)

3 of 22  
Drug NameANUSOL HC
Active IngredientHYDROCORTISONE
CompanySALIX PHARMS (Application Number: A088250)

4 of 22  
Drug NameCOLOCORT
Active IngredientHYDROCORTISONE
CompanyPADDOCK LLC (Application Number: A075172)

5 of 22  
Drug NameCORTEF
Active IngredientHYDROCORTISONE
CompanyPHARMACIA AND UPJOHN (Application Number: N008697)

6 of 22  
Drug NameCORTENEMA
Active IngredientHYDROCORTISONE
CompanyANI PHARMS (Application Number: N016199)

7 of 22  
Drug NameHYDROCORTISONE IN ABSORBASE
Active IngredientHYDROCORTISONE
CompanyCMP PHARMA INC (Application Number: A088138)

8 of 22  
Drug NameHYDROCORTISONE
Active IngredientHYDROCORTISONE
CompanyACTAVIS MID ATLANTIC (Application Number: A087795); ACTAVIS MID ATLANTIC (Application Number: A087796); ACTAVIS MID ATLANTIC (Application Number: A089682); FOUGERA PHARMS INC (Application Number: A080693); FOUGERA PHARMS INC (Application Number: A081203); FOUGERA PHARMS INC (Application Number: A089414); FOUGERA PHARMS (Application Number: A040351); FOUGERA PHARMS (Application Number: A080692); HIKMA INTL PHARMS (Application Number: A083365); IMPAX LABS INC (Application Number: A040646); PERRIGO NEW YORK (Application Number: A085025); PERRIGO NEW YORK (Application Number: A085027); PII (Application Number: A207029); RISING PHARMS INC (Application Number: A040879); TARO (Application Number: A040247); TARO (Application Number: A086257); TARO (Application Number: A088799); TEVA PHARMS (Application Number: A074171); VINTAGE PHARMS (Application Number: A040417); VINTAGE PHARMS (Application Number: A040503); VINTAGE (Application Number: A040761)

9 of 22  
Drug NameSTIE-CORT
Active IngredientHYDROCORTISONE
CompanyPERRIGO CO (Application Number: A089074)

10 of 22  
Drug NameTEXACORT
Active IngredientHYDROCORTISONE
CompanyMISSION PHARMA (Application Number: A081271)

11 of 22  
Drug NameACETASOL HC
Active IngredientACETIC ACID, GLACIAL; HYDROCORTISONE
CompanyACTAVIS MID ATLANTIC (Application Number: A087143)

12 of 22  
Drug NameHYDROCORTISONE AND ACETIC ACID
Active IngredientACETIC ACID, GLACIAL; HYDROCORTISONE
CompanyTARO (Application Number: A088759); VINTAGE (Application Number: A040609)

13 of 22  
Drug NameVOSOL HC
Active IngredientACETIC ACID, GLACIAL; HYDROCORTISONE
CompanyHI TECH PHARMA (Application Number: N012770)

14 of 22  
Drug NameXERESE
Active IngredientACYCLOVIR; HYDROCORTISONE
CompanyVALEANT BERMUDA (Application Number: N022436. Patents: 6514980, 7223387)

15 of 22  
Drug NameCIPRO HC
Active IngredientCIPROFLOXACIN HYDROCHLORIDE; HYDROCORTISONE
CompanyNOVARTIS PHARMS CORP (Application Number: N020805)

16 of 22  
Drug NameCORTISPORIN
Active IngredientHYDROCORTISONE ACETATE; NEOMYCIN SULFATE; POLYMYXIN B SULFATE
CompanyMONARCH PHARMS (Application Number: N050218)

17 of 22  
Drug NameCASPORYN HC
Active IngredientHYDROCORTISONE; NEOMYCIN SULFATE; POLYMYXIN B SULFATE
CompanyCASPER PHARMA LLC (Application Number: N060613)

18 of 22  
Drug NameCORTISPORIN
Active IngredientHYDROCORTISONE; NEOMYCIN SULFATE; POLYMYXIN B SULFATE
CompanyMONARCH PHARMS (Application Number: N050479)

19 of 22  
Drug NameNEOMYCIN AND POLYMYXIN B SULFATES AND HYDROCORTISONE
Active IngredientHYDROCORTISONE; NEOMYCIN SULFATE; POLYMYXIN B SULFATE
CompanyAMRING PHARMS (Application Number: A065216); AMRING PHARMS (Application Number: A065219); BAUSCH AND LOMB (Application Number: A064053); SANDOZ INC (Application Number: A062423); SANDOZ INC (Application Number: A062488); SANDOZ INC (Application Number: A062874)

20 of 22  
Drug NameOTICAIR
Active IngredientHYDROCORTISONE; NEOMYCIN SULFATE; POLYMYXIN B SULFATE
CompanyBAUSCH AND LOMB (Application Number: A064065)

21 of 22  
Drug NameCORTISPORIN
Active IngredientBACITRACIN ZINC; HYDROCORTISONE; NEOMYCIN SULFATE; POLYMYXIN B SULFATE
CompanyMONARCH PHARMS (Application Number: N050168)

22 of 22  
Drug NameNEOMYCIN AND POLYMYXIN B SULFATES, BACITRACIN ZINC AND HYDROCORTISONE
Active IngredientBACITRACIN ZINC; HYDROCORTISONE; NEOMYCIN SULFATE; POLYMYXIN B SULFATE
CompanyAKORN (Application Number: A065213); BAUSCH AND LOMB (Application Number: A064068)

4.2 Therapeutic Uses

Anti-Inflammatory Agents, Steroidal

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


MEDICATION (VET): Acute urticaria /can be treated by/ rapid-acting adrenocorticosteroids, eg, hydrocortisone ... .

Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 690


MEDICATION (VET): /USED/ IV, IN PREVENTING OR TREATING ADRENAL FAILURE & SHOCK-LIKE CONDITIONS IN SURGICAL CASES WHICH HAVE BEEN ON CORTICOSTEROIDS, IN ACUTE ALLERGIC REACTIONS...IN POOR SURGICAL RISKS, & IN CASES WHICH HAVE HAD OVERWHELMING SYSTEMIC INFECTIONS...IN DOGS OR CATTLE...

Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 266


MEDICATION (VET) /EXPL:/: 5 Standardbreds and 4 Dutch Warmblood horses /were/ used to examine sensitivity of peripheral tissues to exogenous insulin 24 hours after administration of a single dose of hydrocortisone (0.06 mg/kg), eGH (20 ug/kg), or saline (0.9% NaCl) solution and after long-term administration (11 to 15 days) of eGH to horses. The amounts of metabolized glucose (M) and plasma insulin concentration (I) were determined. Values for M and the M-to-I ratio were significantly higher 24 hours after administration of a single dose of hydrocortisone than after single-dose administration of eGH or saline solution. After long-term administration of eGH, basal I concentration was increased and the mean M-to-I ratio was 22% lower, compared with values for horses treated with saline solution. Increases in M and the M-to-I ratio after a single dose of hydrocortisone imply that short-term hydrocortisone treatment increases glucose use by, and insulin sensitivity of, peripheral tissues. Assuming a single dose of hydrocortisone improves sensitivity of peripheral tissues to insulin, it may be an interesting candidate for use in reducing insulin resistance in peripheral tissues of horses with several disease states.

de Graaf-Roelfsema E et al; Am J Vet Res 66 (11): 1907-13 (2005)


A randomized, placebo-controlled trial on infants with gestation < or = 30 weeks, body weight of 501 to 1250 g, and respiratory failure /was performed/. Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day. Shortly before hydrocortisone treatment, basal and stimulated (ACTH, 0.1 ug/kg) serum cortisols were measured. The study was discontinued early, because of gastrointestinal perforations in the hydrocortisone group (4/25 vs 0/26, P = .05); 3 of the 4 had received indomethacin/ibuprofen. The incidence of bronchopulmonary dysplasia (28% vs placebo 42%, P = 0.28) tended to be lower, and patent ductus arteriosus (36% vs 73%, P = .01) was lower in the hydrocortisone group. The hydrocortisone-treated infants with serum cortisol concentrations above the median had a high risk of gastrointestinal perforation. In infants with cortisol values below the median, hydrocortisone treatment increased survival without bronchopulmonary dysplasia. Serum cortisol concentrations measured shortly after birth may identify those very high-risk infants who may benefit from hydrocortisone supplementation.

Peltoniemi O et al; J Pediatr 146 (5): 632-7 (2005)


Rectal corticosteroids are indicated to induce remission in acute exacerbations of mild to moderate ulcerative colitis, especially the distal forms including ulcerative proctitis, ulcerative proctosigmoiditis, and left-sided ulcerative colitis. They also are used as adjuncts to systemic corticosteroids or other pharmacological therapies in severe disease and in mild to moderate disease extending proximal to the reach of topical therapy. Hydrocortisone enema has proven useful in some cases of ulcerative colitis involving the transverse and ascending colons. Systemic effects, such as adrenal suppression, preclude the use of corticosteroids for long-term or maintenance therapy. /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


Hydrocortisone enema is indicated as an adjunct in the treatment of Crohn's disease (regional enteritis) with left-sided involvement. /NOT included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


Hydrocortisone rectal dosage forms are indicated for treatment of anogenital pruritus. /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


Hydrocortisone suppositories are indicated in the treatment of inflammatory rectal disorders including cryptitis, inflamed hemorrhoids, and proctitis caused by radiation (factitial). /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


Ophthalmic dosage forms of ... hydrocortisone are not commercially available in the US ... .

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 906


Hydrocortisone and acetic acid combination is indicated in the prophylaxis and treatment of seborrheic otitis externa. /NOT included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 937


Hydrocortisone and acetic acid combination is indicated in the prophylaxis and treatment of chronic eczematoid otitis externa. /NOT included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 937


Hydrocortisone and acetic acid combination is indicated in the prophylaxis of external ear canal injections. /NOT included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 937


Topical corticosteroids of low to medium potency /including hydrocortisone/ are indicated in the treatment of corticosteroid-responsive dermatologic disorders. Occlusive dressings also may be required for chronic or severe cases of lichen simplex chronic, psoriasis, eczema, atopic dermatitis, or chronic hand eczema. The more potent topical corticosteroids and/or occlusive dressings may be required for conditions such as discord occlusive dressings may be required for conditions such as discoid lupus erythematosus, lichen planus, granuloma annulare, psoriatic plaques, and psoriasis affecting the palms, soles, elbows or knees. /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 918


Hydrocortisone acetate ... dental paste /is/ indicated for adjunctive treatment and temporary relief of symptoms associated with nonherpetic oral inflammatory and ulcerative lesions, including recurrent aphthous stomatitis. (Formulations of high potency gels and very high potency ointments also are used in the treatment of aphthous stomatitis. /NOT included in US product labeling/). /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 918


The combination of high dose ketoconazole and hydrocortisone is active against androgen independent prostate cancer. Median response times with hydrocortisone tend to be brief but a significant minority of androgen independent prostate cancer patients benefit with extended responses. ... The medical records of 78 patients with androgen independent prostate cancer treated with hydrocortisone between March 1991 and February 1999 were retrospectively reviewed. Baseline clinical and laboratory factors predictive of prolonged response and survival were identified. The median baseline prostate specific antigen before the initiation of hydrocortisone was 25.1. The number of patients with zero, 1 to 3, and more than 3 lesions on bone scan were 25, 35 and 18, respectively. Median and mean time to prostate specific antigen progression was 6.7 and 14.5 months. Median and mean survival time was 38.0 and 42.4 months, respectively. Response time and survival were highly correlated (r = 0.799). A total of 34 (44%) men had a greater than 75% decrease in prostate specific antigen. The median survival times in men with more vs less than a 75% decrease were 60 vs 24 months, respectively. In a Cox proportional hazard regression, prolonged survival was predicted by percent prostate specific antigen decrease, extent of disease on bone scan and baseline prostate specific antigen. Ketoconazole can induce prolonged responses, occasionally lasting for years. Long responses are more likely to occur in men initiating hydrocortisone earlier in the course of disease before the cancer burden becomes excessive.

Scholz M et al; J Urol 173 (6): 1947-52 (2005)


... The effects of hydrocortisone, which promotes sodium retention, in patients with subarachnoid hemorrhage /was examined/. Twenty-eight subarachnoid hemorrhage patients were randomized into 2 groups after direct surgery: group 1 patients without hydrocortisone treatment (n=14) and group 2 patients with hydrocortisone treatment (1200 mg/d for 10 days; n=14). Both groups underwent hypervolemic therapy by aggressive sodium and water replacement. The goal of the hypervolemic therapy was to maintain the serum sodium level >140 mEq/L and the central venous pressure (CVP) within 8 to 12 cm H2O. Group 2 demonstrated a lower sodium excretion (P<0.05) and higher serum sodium level (P<0.05) compared with group 1. Hyponatremia developed in 6 patients (43%) in group 1 and 0 patients in group 2 (P<0.05). Group 2 also demonstrated a lower urine volume, lower infusion volume (P<0.05) required for hypervolemic therapy, and higher CVP (P<0.05). Failure to maintain CVP was observed in 12 patients (86%) in group 1 and 3 patients (21%) in group 2 (P<0.05). Hydrocortisone caused no serious side effects. Hydrocortisone clearly attenuates excessive natriuresis. Prophylactic hydrocortisone administration appears to have a therapeutic value in inducing hypervolemia efficiently after SAH.

Moro N, Katayama Y; Stroke 34 (12): 2807-11 (2003)


... This study presents the first results on the impact of hydrocortisone administration in norepinephrine dependent severely burned patients. In a prospective cohort study fourteen consecutive severely burned patients received, 12 hr after norepinephrine dependency, a hydrocortisone bolus of 100 mg followed by 0.18 mg/(kg hr) hydrocortisone. The course of the necessary norepinephrine dose, as well as the fluid balance was documented 12 hr prior and after the first dosage of hydrocortisone. Statistical analysis showed an unexpected increase of the required norepinephrine dosage. A statistical post hoc evaluation of surviving and non-surviving patients revealed a significant increase of norepinephrine in non-survivors whereas in survivors it was possible to reduce norepinephrine significantly. Furthermore, the median fluid requirement of surviving patients could be significantly reduced in the group of non-survivors there was no change of volume needed. Data suggests that /the/ hydrocortisone might be useful in selected patients with severe burn injuries. However, patients not responding to hydrocortisone administrations seem to have a poor prognosis. Findings are in contrast to previously published data on septic patients, in whom hydrocortisone administration resulted in a reduction of norepinephrine.

Winter W et al; Burns 29 (7): 717-20 (2003)


In this controlled study we examined whether exogenously administered stress doses of hydrocortisone during cardiac surgery reduce perioperative stress exposure and the long-term incidence of chronic stress symptoms and improve health-related quality of life after cardiac surgery. Thirty-six high-risk patients undergoing cardiac surgery were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Of 28 available patients at 6 months after cardiac surgery, 14 had received hydrocortisone, and 14 had received placebo. Traumatic memories, chronic stress symptoms (posttraumatic stress disorder scores), and health-related quality of life were measured by using validated questionnaires. Compared with patients from the placebo group, patients from the hydrocortisone group had a significantly shorter duration of intensive care unit treatment, required lower doses of the stress hormone norepinephrine during cardiac surgery, and had significantly fewer stress symptoms and a better health-related quality of life regarding physical function, chronic pain, general health, vitality, and mental health during follow-up. The groups did not differ with regard to the number or type of intensive care unit-related traumatic memories. The use of stress doses of hydrocortisone in high-risk cardiac surgical patients reduces perioperative stress exposure, decreases chronic stress symptoms, and improves health-related quality of life at 6 months after cardiac surgery.

Weis F et al; J Thorac Cardiovasc Surg 131 (2): 277-82 (2006)


In salt-losing forms of congenital adrenogenital syndrome ... hydrocortisone is administered in conjunction with liberal salt intake. Because of the risk of growth retardation with excessive dosage, the minimum dosage of the corticosteroid required to suppress adrenocortical hyperfunction should be used. If sodium loss and hypotension are not adequately controlled by ... hydrocortisone, an additional mineralocorticoid drug should be given. Mineralocorticoid replacement can usually be discontinued in children 5-7 years of age, but a glucocorticoid must be continued throughout life.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3024


In moderate dosages, glucocorticoids promote a reduction in serum calcium concentrations and are effective in the treatment of hypercalcemia resulting from sarcoidosis or vitamin D intoxication. Hypercalcemia associated with bone involvement in multiple myeloma can usually be ameliorated with glucocorticoids, and the drugs are the most effective long-term treatment for hypercalcemia associated with breast cancer in postmenopausal women. Although glucocorticoids may occasionally be of value in the treatment of hypercalcemia associated with other malignancies, good results are not always obtained and the drugs should be reserved for patients refractory to other therapy. Glucocorticoids are not effective in hypercalcemia caused by hyperparathyroidism. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3024


Corticosteroids are administered in physiologic dosages to replace deficient endogenous hormones in patients with adrenocortical insufficiency. Because production of both mineralocorticoids and glucocorticoids is deficient in these patients, hydrocortisone ... is usually the corticosteroid of choice for replacement therapy. Concomitant administration of a more potent mineralocorticoid (fludrocortisone) may be required in some patients. ... In shock caused by acute adrenocortical insufficiency, IV administration of hydrocortisone (or a synthetic glucocorticoid) in conjunction with other therapy for shock is essential.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3024


... A randomized-controlled trial /was conducted/ to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic hydrocortisone in reducing treatment of hypotension in extremely low birth weight infants. Infants were assigned to receive either hydrocortisone or placebo within the first 3 hours of life. Therapy was continued for 5 days. The presence of hypotension was based on an operational definition and treatment with vasopressors was standardized based on an a priori protocol. A total of 34 patients were enrolled. Baseline characteristics were similar between groups. Of the hydrocortisone group 25% received vasopressor at 24 hours of age compared to 44% of the placebo group. On day of life 2, only 7% of the hydrocortisone group received vasopressor compared to 39% of the placebo group (p<0.05). Prophylactic treatment with hydrocortisone reduces the incidence of hypotension, defined by treatment with vasopressor, among extremely low birth weight infants during the first 2 days of life. However, the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to extremely low birth weight infants makes hydrocortisone prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established.

Efird MM et al; J Perinatol 25 (2): 119-24 (2005)


4.3 Drug Warning

It is not known whether rectal corticosteroids are distributed into breast milk. Systemic corticosteroids are distributed into breast milk and may cause unwanted effects, such as growth suppression, in the infant. Rectal corticosteroids are not recommended for use by breast-feeding mothers. /Corticosteroids, rectal/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


The results of a prospective randomized controlled trial, which looked at the incidence of postoperative diabetes insipidus following the use of three different hydrocortisone protocols, and the results of a study, on the incidence of diabetes insipidus and cortisol response in patients not given hydrocortisone /was reported/. In study 1, 114 patients with pituitary macroadenoma were randomized into three groups: conventional dose (injected hydrocortisone 100 mg IV 6-hourly for 3 days); intermediate dose (injected hydrocortisone 100 mg IV 6-hourly on day 1, 100 mg IV 8-hourly on day 2, and 100 mg IV 12-hourly on day 3); low dose protocol (injected hydrocortisone 25 mg IV 6-hourly on day 1, 25 mg IV 8-hourly on day 2 and 25 mg IV 12-hourly on day 3). Radical excision was achieved in 92 patients. The incidence of diabetes insipidus with the conventional dose was 52%, intermediate dose, 36% and low dose, 24% (p = 0.025). Study 2 included 16 consecutive patients with Hardy's grade A & B pituitary adenoma. These patients were randomized to receive (Group I) or not receive (Group II) hydrocortisone. Patients in Group II demonstrated normal cortisol response intraoperatively and no patient developed features of hypocortisolism; the incidence of diabetes insipidus in this group was 14%. The low dose hydrocortisone protocol reduced the incidence of diabetes insipidus by 46% when compared with the conventional dose hydrocortisone protocol. In patients with grade A and B tumor with normal preoperative cortisol levels, the use of perioperative hydrocortisone can be avoided.

Rajaratnam S et al; Br J Neurosurg 17 (5): 437-42 (2003)


ACUTE ADRENAL INSUFFICIENCY RESULTS FROM TOO RAPID WITHDRAWAL OF CORTICOSTEROID THERAPY. /CORTICOSTEROIDS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1496


POTENTIAL ADVERSE EFFECTS ON FETUS: Cleft palate, spontaneous abortions, and intrauterine growth retardation in animals. Potential for cleft palate formation and adrenal suppression in humans, although teratogenic effects have not been confirmed. POTENTIAL SIDE EFFECTS ON BREAST-FED INFANT: Passes into breast milk in small amounts. Administration of physiologic doses unlikely to adversely affect infant. FDA Category: C (C = Studies in laboratory animals have revealed adverse effects on the fetus (teratogenic, embryocidal, etc.) but there are no controlled studies in pregnant women. The benefits from use of the drug in pregnant women may be acceptable despite its potential risks, or there are no laboratory animal studies or adequate studies in pregnant women.) /Adrenocorticosteroids/ /from table II/

Stockton DL, Palle AS; J Am Acad Dermatol 23 (1): 87-103 (1990)


FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./ /Hydrocortisone acetate/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


Use of preparations containing benzyl alcohol is not recommended in neonates. A fatal toxic syndrome consisting of metabolic acidosis, central nervous system depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with this use. /Hydrocortisone acetate, Hydrocortisone sodium phosphate, or Hydrocortisone sodium succinate injections/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 957


This study examined the hypothesis/ that subjects with posttraumatic stress disorder, as compared to nonpsychiatric controls, would show greater impairments in verbal declarative memory and working memory, but not attention, following exogenous glucocorticoid administration. ... Under double-blind randomized crossover conditions, 17-mg hydrocortisone or placebo was administered by intravenous (iv) bolus to 15 medication-free posttraumatic stress disorder subjects (4 female) and 12 nonpsychiatric control subjects (4 female) matched by age, sex, and education level. Participants then underwent positron emission tomography (PET) scanning and 90 min after the initial drug/placebo administration, cognitive testing was then performed. By repeated measures ANCOVA (covaried for baseline performance on that neuropsychological test), neither attention tasks of digit span forward nor backward showed significant change. However, there were significant drug (F = 17.644, df = 1,25 P < 0.001), group (F = 4.383, df = 1,25 P = 0.048), and drug by group interactions (F = 4.756, df = 1,25 P = 0.040) for verbal declarative memory. By t-test, there was not a difference in baseline performance on this measure between subject groups. The subject group with posttraumatic stress disorder experienced a greater decline in verbal declarative memory performance following hydrocortisone administration. For working memory, there were significant group (F = 6.048, df = 1,25 P = 0.022) and drug by group interactions (F = 6.048, df = 1,25 P = 0.022) for verbal declarative memory. By t-test, there was not a difference in baseline performance on this measure between subject groups. The hydrocortisone administration led to impairment in working memory in the group of subjects with posttraumatic stress disorder, but not in the control subject group.

Grossman R et al; Ann N Y Acad Sci 1071: 410-21(2006)


Because certain areas of the body may be more susceptible to atrophic changes than others following treatment with corticosteroids, certain topical corticosteroid preparations (e.g., ... hydrocortisone valerate 0.2% cream; ...) should not be applied to the face or intertriginous areas (e.g., axilla, groin). ./Hydrocortisone valerate/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3524


Patients receiving topical corticosteroids should be instructed to use the preparations only as directed by the physician, only for the disorder for which it was prescribed, and for no longer than the time period prescribed. Unless occlusive dressings are part of the prescribed regimen, patients should be instructed that treated areas of skin should not be bandaged or otherwise covered or wrapped as to be occlusive. Occlusive dressings (including flurandrenolide tape) should not be used on weeping or exudative lesions, and flurandrenolide tape should not be used in intertriginous areas. Because thermal homeostasis may be impaired when occlusive dressings cover large areas, they should be removed if body temperature increases. /Topical Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3524


Rectal corticosteroid therapy should be used with caution in patients with severe ulcerative disease, and only after adequate proctologic examination, because of the risk of intestinal perforation. Rectal corticosteroid therapy is contraindicated in patients with intestinal obstruction, abscess, impending perforation, peritonitis, extensive fistulas, and fresh intestinal anastomoses or sinus tracts. /Topical corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525


The immunosuppressive effects of corticosteroids may be associated with impairment of the normal function of T cells and macrophages; such impairment may result in activation of latent infection or exacerbation of intercurrent infections, including those caused by Candida, Mycobacterium, Toxoplasma, Strongyloides, Pneumocystis, Cryptococcus, Nocardia, and ameba. Corticosteroid-containing preparations should be used with caution in patients with impaired T-cell function or in those receiving other immunosuppressive therapy. /Topical corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525


Topical corticosteroids should not be used in patients with markedly impaired circulation since skin ulceration has occurred in these patients following use of the drugs. /Topical corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3524


If skin irritation or contact dermatitis occurs during topical corticosteroid therapy, the drug should be discontinued and appropriate therapy initiated. It should be kept in mind that occlusive plastic dressings rarely may cause local or hypersensitivity reactions. /Topical corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3524


Assessment of patients on steroid replacement therapy is important to avoid the consequences of overtreatment such as osteoporosis. The aim of this prospective study is to evaluate the severity and the etiology of osteopenia in 24 patients (15 women, 9 men) with Addison's disease receiving 30 mg hydrocortisone. Mean age of patients was 55 15 years. Osteoporosis, diagnosed by the measurement of bone mineral density at the level of lumbar spine and right hip, was found in 58% of patients, i.e. in 10 women and 4 men. The latter had normal testosterone levels while seven women had an early menopause, the etiology of their Addison's disease being autoimmune. Three were on hormonotherapy. Correlations were found between bone mineral density in the femoral neck and hip and the dose of hydrocortisone (mg/m(2)/day; mg/kg/day), the duration of treatment and 24 hr-cortisoluria/g creatinine. Multivariate analysis shows that 24-hr cortisoluria/g creatinine is a good predictor of bone mineral density values. Thus, osteoporosis is frequent in Addison's disease and cortisoluria could be a useful tool to predict this complication.

Heureux F et al; Ann Endocrinol (Paris) 61 (3): 179-83 (2000)


/Subjects/ 18 to 55 years old with chronic fatigue syndrome and no medical or psychiatric illness requiring medication, were randomized in a double blind, placebo controlled trial to receive oral hydrocortisone, 13 mg/sq m body surface area every morning and 3 mg/sq m every afternoon (25 to 35 mg/day, equivalent to about 7.5 mg prednisone/day) or placebo for 12 weeks. Before and after treatment bone mineral density of the lumbar spine was measured by dual energy x-ray absorptiometry. We studied 23 subjects (19 women, 4 men). For the 11 hydrocortisone recipients there was a mean decrease in bone mineral density: mean change from baseline of the lateral spine was -2.0% (95% CI -3.5 to -0.6. p = 0.03) and mean change of the anteroposterior spine was -0.8% (95% CI -1.5 to -0.1, p = 0.06). Corresponding changes for the 12 placebo recipients were +1.0% (95% CI -1.0 to 3.0, p = 0.34) and +0.2% (95% CI -1.4 to 1.5, p = 0.76). A 12 week course of low dose glucocorticoids given to ambulatory subjects with chronic fatigue syndrome was associated with a decrease in bone mineral density of the lumbar spine. This decrease was statistically significant in lateral spine measurements and nearly so in anteroposterior spine measurements.

McKenzie R et al; J Rheumatol 27 (9): 2222-6 (2000)


Adverse neurologic effects of glucocorticoids have included headache, vertigo, insomnia, restlessness and increased motor activity, ischemic neuropathy, EEG abnormalities, and seizures. Glucocorticoids may precipitate mental disturbances ranging from euphoria, mood swings, depression and anxiety, and personality changes to frank psychoses. Emotional instability or psychotic tendencies may be aggravated by the drugs. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has been reported, generally in association with withdrawal of glucocorticoid therapy. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3034


Adverse GI effects of corticosteroids include nausea, vomiting, anorexia which may result in weight loss, increased appetite which may result in weight gain, diarrhea or constipation, abdominal distension, pancreatitis, gastric irritation, and ulcerative esophagitis. Corticosteroids have been implicated in the development, reactivation, perforation, hemorrhage, and delayed healing of peptic ulcers. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3034


When glucocorticoids are administered over a prolonged period, they may produce various endocrine disorders including hypercorticism (cushingoid state) and amenorrhea or other menstrual difficulties. Corticosteroids may decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus especially in patients predisposed to diabetes mellitus. If steroid therapy is required in patients with diabetes mellitus, changes in insulin or oral antidiabetic agent dosage or diet may be necessary. Corticosteroids have also been reported to increase or decrease motility and number of sperm in some men. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3034


Sodium retention with resultant edema, potassium loss, hypokalemic alkalosis, and hypertension may occur in patients receiving glucocorticoids. Congestive heart failure may occur in susceptible patients. ... Dietary salt restriction is advisable and potassium supplementation may be necessary in patients receiving hydrocortisone or cortisone for its anti-inflammatory or immunosuppressant effects. When glucocorticoids with substantial mineralocorticoid activity are administered, patients should be instructed to notify their physicians if edema develops. All glucocorticoids increase calcium excretion and may cause hypocalcemia.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3033


Because anaphylactoid reactions have occurred in patients receiving glucocorticoids parenterally, precautionary measures should be taken prior to parenteral administration of the drugs, particularly in patients with history of a drug allergy. Some patients who appear to be hypersensitive to parenteral glucocorticoids may actually be hypersensitive to the paraben preservatives present in some injectable formulations. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3034


Patients who become immunosuppressed while receiving glucocorticoids have increased susceptibility to infections compared with healthy individuals. Some infections such as varicella (chickenpox) and measles can have a more serious or even fatal outcome in such patients, particularly in children. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3033


Muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones are manifestations of protein catabolism which may occur during prolonged therapy with glucocorticoids. These adverse effects may be especially serious in geriatric or debilitated patients. Before initiating glucocorticoid therapy in postmenopausal women, the fact that they are especially prone to osteoporosis should be considered. Glucocorticoids should be withdrawn if osteoporosis develops, unless their use is life-saving. A high-protein diet may help to prevent adverse effects associated with protein catabolism. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3032


Some commercially available formulations of ... hydrocortisone ... contain sulfites that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3034


Because corticosteroids inhibit antibody response, the drugs may cause a diminished response to toxoids and live or inactivated vaccines. In addition, corticosteroids may potentiate replication of some organisms contained in live, attenuated vaccines and supraphysiologic dosages of the drugs can aggravate neurologic reactions to some vaccines. Routine administration of vaccines or toxoids should generally be deferred until corticosteroid therapy is discontinued. Administration of live virus or live, attenuated vaccines, including smallpox vaccine, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids. In addition, if inactivated vaccines are administered to such patients, expected serum antibody response may not be obtained. The Public Health Service Advisory Committee on Immunization Practices (ACIP) and American Academy of Family Physicians (AAFP) state that administration of live virus vaccines usually is not contraindicated in patients receiving corticosteroid therapy as short-term (less than 2 weeks) treatment, in low to moderate dosages, as long-term alternate-day treatment with short-acting preparations, in maintenance physiologic dosages (replacement therapy), or if corticosteroids are administered topically, ophthalmically, intra-articularly, bursally, or into a tendon. If immunization is necessary in a patient receiving corticosteroid therapy, serologic testing may be needed to ensure adequate antibody response and additional doses of the vaccine or toxoid may be necessary. Immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of glucocorticoids or in patients receiving glucocorticoids as replacement therapy (e.g., Addison's disease). /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3036


High dosages of glucocorticoids in children may cause acute pancreatitis leading to pancreatic destruction. Children have developed increases in intracranial pressure (pseudotumor cerebri), causing papilledema, oculomotor or abducens nerve paralysis, visual loss, and headache. Pseudotumor cerebri has occurred most frequently following reduction of dosage or a change in the steroid administered. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3035


Long-term administration of pharmacologic dosages of glucocorticoids to children should be avoided if possible, since the drugs may retard bone growth when administered by any route. If prolonged therapy is necessary, the growth and development of infants and children should be closely monitored, and the potential effects on growth should be weighed against clinical benefits and the availability of alternative therapy. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3035


Because glucocorticoids increase susceptibility to and mask symptoms of infection, the drugs should not be used, except in life-threatening situations, in patients with viral infections or bacterial infections not controlled by anti-infectives. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3035


Glucocorticoids may cause fetal damage when administered to pregnant women. One retrospective study of 260 women who received pharmacologic dosages of glucocorticoids during pregnancy revealed 2 instances of cleft palate, 8 stillbirths, 1 spontaneous abortion, and 15 premature births. Another study reported 2 cases of cleft palate in 86 births. Occurrence of cleft palate in these studies is higher than in the general population but could have resulted from the underlying diseases as well as from the steroids. Other fetal abnormalities that have been reported following glucocorticoid administration in pregnant women include hydrocephalus and gastroschisis. Women should be instructed to inform their physicians if they become or wish to become pregnant while receiving glucocorticoids. If glucocorticoids must be used during pregnancy or if the patient becomes pregnant while taking one of these drugs, the potential risks should be carefully considered. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3035


Netherton syndrome is a congenital skin disease associated with decreased skin barrier function and increased percutaneous absorption. A case of an 11-year-old boy with Netherton syndrome who developed Cushing syndrome after application of 1% hydrocortisone ointment to his entire body for more than 1 year /is reported/. This presentation illustrates that even low-potency steroid ointments should be used with caution in Netherton syndrome and warns about the use of long-term topical medications with potential systemic side effects when used in large quantities in any chronic skin disease.

Halverstam CP et al; Pediatr Dermatol 24 (1): 42-5 (2007)


A 40 Year-old woman, during hospitalisation for severe acute asthma, presented with an allergy to hydrocortisone hemisuccinate in the form of generalized pruritus with, on examination, cutaneous mucosal lesions in the form of purpura and ecchymoses on the abdomen and the upper and lower limbs. The substitution of hydrocortisone hemisuccinate led to the return to normal. /Hydrocortisone hemisuccinate/

El Mekki F et al; Presse Med 33(9 Pt 1): 604-6 (2004)


Assessment of patients on steroid replacement therapy is important to avoid the consequences of overtreatment such as osteoporosis. The aim of this prospective study is to evaluate the severity and the etiology of osteopenia in 24 patients (15 women, 9 men) with Addison's disease receiving 30 mg hydrocortisone. Mean age of patients was 55 15 years. Osteoporosis, diagnosed by the measurement of bone mineral density at the level of lumbar spine and right hip, was found in 58% of patients, i.e. in 10 women and 4 men. The latter had normal testosterone levels while seven women had an early menopause, the etiology of their Addison's disease being autoimmune. Three were on hormonotherapy. Correlations were found between bone mineral density in the femoral neck and hip and the dose of hydrocortisone (mg/m(2)/day; mg/kg/day), the duration of treatment and 24 hr-cortisoluria/g creatinine. Multivariate analysis shows that 24-hr cortisoluria/g creatinine is a good predictor of bone mineral density values. Thus, osteoporosis is frequent in Addison's disease and cortisoluria could be a useful tool to predict this complication.

Heureux F et al; Ann Endocrinol (Paris) 61 (3): 179-83 (2000)


4.4 Drug Indication

For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.


FDA Label


Treatment of adrenal insufficiency in adults.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.


Therapeutic Hydrocortisone is a synthetic or semisynthetic analog of natural hydrocortisone hormone produced by the adrenal glands with primary glucocorticoid and minor mineralocorticoid effects. As a glucocorticoid receptor agonist, hydrocortisone promotes protein catabolism, gluconeogenesis, capillary wall stability, renal excretion of calcium, and suppresses immune and inflammatory responses. (NCI04)


5.2 MeSH Pharmacological Classification

Anti-Inflammatory Agents

Substances that reduce or suppress INFLAMMATION.


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety

HYDROCORTISONE


5.3.2 FDA UNII

WI4X0X7BPJ


5.3.3 Pharmacological Classes

Established Pharmacologic Class [EPC]

Corticosteroid


Mechanisms of Action [MoA]

Corticosteroid Hormone Receptor Agonists


5.4 ATC Code

Anatomical main group: H - Systemic hormonal prep, excluding sex hormones
Therapeutic subgroup: H02 - Corticosteroids for systemic use
Pharmacological subgroup: H02A - Corticosteroids for systemic use, plain
Chemical subgroup: H02AB - Glucocorticoids
Chemical substance: H02AB09 - Hydrocortisone


A - Alimentary tract and metabolism
A01 - Stomatological preparations
A01A - Stomatological preparations
A01AC - Corticosteroids for local oral treatment
A01AC03 - Hydrocortisone


A - Alimentary tract and metabolism
A07 - Antidiarrheals, intestinal antiinflammatory/antiinfective agents
A07E - Intestinal antiinflammatory agents
A07EA - Corticosteroids acting locally
A07EA02 - Hydrocortisone


C - Cardiovascular system
C05 - Vasoprotectives
C05A - Agents for treatment of hemorrhoids and anal fissures for topical use
C05AA - Corticosteroids
C05AA01 - Hydrocortisone


D - Dermatologicals
D07 - Corticosteroids, dermatological preparations
D07A - Corticosteroids, plain
D07AA - Corticosteroids, weak (group i)
D07AA02 - Hydrocortisone


D - Dermatologicals
D07 - Corticosteroids, dermatological preparations
D07X - Corticosteroids, other combinations
D07XA - Corticosteroids, weak, other combinations
D07XA01 - Hydrocortisone


H - Systemic hormonal preparations, excl. sex hormones and insulins
H02 - Corticosteroids for systemic use
H02A - Corticosteroids for systemic use, plain
H02AB - Glucocorticoids
H02AB09 - Hydrocortisone


S - Sensory organs
S01 - Ophthalmologicals
S01B - Antiinflammatory agents
S01BA - Corticosteroids, plain
S01BA02 - Hydrocortisone


S - Sensory organs
S01 - Ophthalmologicals
S01C - Antiinflammatory agents and antiinfectives in combination
S01CB - Corticosteroids/antiinfectives/mydriatics in combination
S01CB03 - Hydrocortisone


S - Sensory organs
S02 - Otologicals
S02B - Corticosteroids
S02BA - Corticosteroids
S02BA01 - Hydrocortisone


5.5 Absorption, Distribution and Excretion

Absorption

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.


Route of Elimination

Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.


Following percutaneous penetration of a topical corticosteroid, the drug that is systemically absorbed probably follows the metabolic pathways of systemically administered corticosteroids. Corticosteroids usually are metabolized in the liver and excreted by the kidneys. Some topical corticosteroids and their metabolites are excreted in bile. /Topical corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525


Topical application of corticosteroids to the mucosa of the genitourinary or lower intestinal tract may result in substantial systemic absorption of the drugs. In healthy individuals, as much as 30-90% of rectally administered hydrocortisone as a retention enema may be absorbed. Greater amounts of hydrocortisone may be absorbed rectally if the intestinal mucosa is inflamed.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525


Following topical application of a corticosteroid to most areas of normal skin, only minimal amounts of the drug reach the dermis and subsequently the systemic circulation; however, absorption is markedly increased when the skin has lost its keratin layer and can be increased by inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema). The drugs are absorbed to a greater degree from the scrotum, axilla, eyelid, face, and scalp than from the forearm, knee, elbow, palm, and sole. Even after washing the area being treated, prolonged absorption of the corticosteroid occurs, possibly because the drug is retained in the stratum corneum. /Topical corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525


Percutaneous penetration of corticosteroids varies among individual patients and can be increased by the use of occlusive dressings, by increasing the concentration of the corticosteroid, and by using different vehicles. The use of an occlusive dressing with hydrocortisone for 96 hours substantially enhances percutaneous penetration of the drug; however, such use for up to 24 hours does not appear to alter penetration of topically applied hydrocortisone.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525


The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam were determined after single and multiple dosing in healthy subjects as well as in patients with inflammatory bowel disease. Endogenous hydrocortisone was suppressed by dexamethasone administration. Plasma levels were compared with those observed after intravenous administration of hydrocortisone. Only a very small part of the rectal dose (100 mg) was absorbed; the mean absolute bioavailability was 3.1% in healthy volunteers and 4.5% in patients. There was substantial intersubject variability. Although maximum hydrocortisone levels after single or multiple doses were significantly higher (about 70%) in the patient group, the systemic bioavailability is very low so that the risk of systemic side effects after rectal administration of hydrocortisone acetate foam has to be considered very low. /Hydrocortisone acetate/

Tromm A et al; J Clin Pharmacol 41 (5): 536-41 (2001)


Partially absorbed following rectal administration. In ulcerative colitis patients, up to 50% /of hydrocortisone/ may be absorbed.

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


In normal healthy subjects, approximately 26% of the dose is absorbed following rectal administration of a suppository. However, absorption across abraded or inflamed surfaces may be increased. Systemic absorption may be greater from the foam dosage form than from the enema, because the foam is not expelled. /Hydrocortisone acetate/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 913


The hydrocortisone pharmacokinetic profiles of hydrocortisone acetate foam administered rectally was assessed in healthy volunteers and patients with ulcerative colitis or X-irradiation colitis. Endogenous production of hydrocortisone was suppressed by dexamethasone. Comparison of these data with those obtained after intravenous administration enabled assessment of absolute bioavailability, which was 30.0 + or - 15.1% in healthy volunteers vs. 16.4 + or - 14.8% in patients (P = 0.09). Maximal concentrations of hydrocortisone were also decreased in patients, 277 + or - 215 nmol/L vs. 610 + or - 334 nmol/L (P = 0.03). There was a nonsignificant tendency to faster absorption of hydrocortisone in patients vs. healthy volunteers, as the times to peak concentration were, respectively, 2.5 + or - 1.2 hr vs. 2.8 + or - 0.8 hr (P = 0.64), and the mean absorption times were 1.96 + or - 1.45 hr vs. 2.54 + or - 1.62 hr (P = 0.46). /Hydrocortisone acetate/

Petitjean O et al; Aliment Pharmacol Ther 6 (3): 351-7 (1992)


The pharmacokinetics of 20 mg hydrocortisone were studied after IV and oral administration. Endogenous hydrocortisone was suppressed by dexamethasone administration. Hydrocortisone concentrations were measured in plasma and saliva. ... The volume of distribution was 34 L. Oral bioavailability averaged 96%. Absorption was rapid, achieving maximum hydrocortisone levels of 300 ng/mL after 1 hour. Saliva levels were not proportional to plasma levels, but could be shown to reflect free, non-protein bound hydrocortisone concentrations in plasma.

Derendorf H et al; J Clin Pharmacol 31 (5): 473-6 (1991)


20 canine skin samples /were/ obtained from the thorax, neck, and groin regions of 5 Greyhounds ... after euthanasia and stored at -20 degrees C until required. The skin was then defrosted and placed into diffusion cells, which were maintained at approximately 32 degrees C by a water bath. Saturated solutions of hydrocortisone that contained trace amounts of radiolabelled (14)C-hydrocortisone in each vehicle (ie, PBS solution (PBSS) alone, 50% ethanol (EtOH) in PBSS (wt/wt), and 50% propylene glycol in PBSS [wt/wt]) were applied to the outer (stratum corneum) surface of each skin sample, and aliquots of receptor fluid were collected for 24 hours and analyzed for hydrocortisone. The maximum flux of hydrocortisone was significantly higher for all sites when dissolved in a vehicle containing 50% EtOH, compared with PBSS alone or 50% propylene glycol, with differences more prominent in skin from the neck region. In contrast, higher residues of hydrocortisone were found remaining within the skin when PBSS alone was used as a vehicle, particularly in skin from the thorax and neck. Penetration of topically applied hydrocortisone is enhanced when EtOH is used in vehicle formulation. Significant regional differences (ie, among the thorax, neck, and groin areas) are also found in the transdermal penetration and skin retention of hydrocortisone. Variability in clinical response to hydrocortisone can be expected in relation to formulation design and site of application.

Mills PC et al; Am J Vet Res 66 (1): 43-7 (2005)


Skin was harvested from the thorax, groin and leg (dorsal metacarpal) regions of five Thoroughbred geldings and frozen (-20 degrees C) until required. Defrosted skin was placed in Franz-type diffusion cells and the amount of radiolabelled ((3)H) hydrocortisone, in a saturated solution of unlabelled hydrocortisone in 50% ethanol (w/w), which penetrated through and remained within skin samples was measured over 24 hr. Significantly higher (P < 0.001) maximum flux (J(max); mol/cm(2)/hr) was measured when hydrocortisone was applied to skin from the leg, compared to thorax and groin, although significantly less hydrocortisone (P < 0.001) was retained within skin from the leg at 24 hr. Topical application of hydrocortisone in a vehicle containing ethanol would penetrate faster through leg skin from the lower leg when compared with the thorax or groin, which depending on cutaneous blood flow, may result in higher systemic drug concentrations or greater efficiency in treating local inflamed tissue.

Cross SE et al; J Vet Pharmacol Ther 29 (1): 25-30 (2006)


Subcellular distribution of (3)H-hydrocortisone and its metabolites in the liver and kidney of intact and alloxan diabetic rats was investigated. Ten minutes after the administration of this hormone several metabolites (mostly tetrahydrocortisol) and the native hormone were found in liver cytosol, microsomes, mitochondria and nuclei, the relative content of individual compounds in various subcellular fractions being different. In liver mitochondria, microsomes and nuclei of alloxan diabetic rats the concentration of tetrahydrocortisol was decreased, while that of native hormone was increased as compared to normal animals. ... . In kidney cytosol and microsomes of intact rats cortisone and tetrahydrocortisol were found. In diabetic animals, however, the concentration of tetrahydrocortisol increased, while that of cortisone was undetectable.

Minchenko AG, Tronjko ND; Endocrinol Exp 22 (1): 19-28 (1988)


Hydrocortisone distribution over the three main components of blood, i.e., plasma water, plasma proteins, and erythrocytes, was studied in vitro at various hydrocortisone concentrations in plasma, in a suspension of washed erythrocytes in plasma water, and in whole blood. The distribution ratio of hydrocortisone in the system of erythrocytes in plasma water was 2.1 when hydrocortisone, 0.18-10.8 ug/mL, was added. In whole blood, however, this ratio was 2.4 for the same concentration range. In the hydrocortisone range of 0.18-0.68 ug/mL of whole blood, the uptake percentage of hydrocortisone by erythrocytes increased from about 16 to 28% of the amount of hydrocortisone added. By adding blank ultrafiltrate to hydrocortisone-enriched blood, it appeared that the erythrocyte fraction released hydrocortisone in overproportional quantities compared with the release by plasma proteins. ... Migration of HC from hydrocortisone-spiked plasma to blank erythrocytes reached an equilibrium within 5 min.

Driessen O et al; Ther Drug Monit 11 (4): 401-7 (1989)


We investigated the influence of dose distribution in hydrocortisone replacement therapy on urine free cortisol excretion. To this end, we measured 24-hr urine free cortisol (24-hr UFC) in 13 patients with hypocortisolism. The patients took 25 mg hydrocortisone/day according to the following schedules: either a single 25 mg hydrocortisone dose at 8:00 a.m., or 15 mg hydrocortisone at 8:00 a.m. and 10 mg hydrocortisone at 2:00 p.m., or 5 mg hydrocortisone at 8:00 a.m., 10:00 a.m., 2:00 p.m., 6:00 p.m. and 10:00 p.m. 24-hr UFC decreased significantly with increasing division of the daily 25 mg hydrocortisone dose. When taking 25 mg hydrocortisone in a single morning dose, the mean 24-hr UFC was 649 + or - 52 nmol/day (mean + or - SEM). When the daily dose was divided into doses of 15 mg and 10 mg hydrocortisone, 24-hr UFC was reduced by 28 % to 466 + or - 39 nmol/day (p < 0.002). After division into five doses of 5 mg, 24-hr UFC was reduced by 42.8 % to 371 + or - 36 nmol/day (p < 0.001) compared to the single 25 mg dose. These data demonstrate that consideration of the dose distribution in hydrocortisone replacement therapy when analysing 24-hr UFC is of clinical importance.

Bliesener N et al; Exp Clin Endocrinol Diabetes 111 (7): 443-6 (2003)


Rabbit ear was single-pass perfused with protein-free buffer solution at a rate of 0.02 mL/min per sq cm surface area for up to 6 hr. Hydrocortisone or hydrocortisone 21-butyrate or hydrocortisone 21-hemisuccinate was applied dermally (0.01-1.0% w/w) in suspension with isopropyl myristate or dissolved in 1,2-propanediol. The ointments were stiffened with 5% polyethylene 1500 or 1.2% methylcellulose respectively. Hydrocortisone was slowly absorbed and did not reach a steady-state absorption rate during the experimental period. No metabolites of hydrocortisone were found during ear perfusion. In the supernatant of skin homogenate, however, cortisone, hydrocortisone-20 alpha-ol and another, as yet unidentified metabolite, were observed. Hydrocortisone 21-butyrate was completely hydrolyzed during dermal absorption, showing steady-state concentrations of hydrocortisone in the effluent. Hydrocortisone 21-hemisuccinate did not reach steady-state concentrations in the effluent. About two-thirds was hydrolyzed during absorption. During arterial perfusion approximately 30% of hydrocortisone 21-butyrate was hydrolyzed whereas 97% of hydrocortisone 21-hemisuccinate remained intact. First-pass ester hydrolysis in skin may be complete for the poorly absorbed glucocorticoids leading to metabolites of less lipophilicity.

Bast GE, Kampffmeyer HG; Xenobiotica 24 (10): 1029-42 (1994)


5.6 Metabolism/Metabolites

Metabolism

Primarily hepatic via CYP3A4


A study was made of the absorption of exogenous hydrocortisone and formation of its metabolites in isolated liver of intact and exposed rats in conditions of recirculating perfusion. It was shown that the absorption of the hormone by the liver of irradiated rats was greatly lowered but the content of most metabolites found in the perfused medium of irradiated liver increased as compared to the control. It is suggested that irradiation inhibits subsequent transformations of the hydrocortisone metabolism products.

Litskevich LA, Dokshina GA; Radiobiologiia 25 (2): 200-3 (1985)


Subcellular distribution of (3)H-hydrocortisone and its metabolites in the liver and kidney of intact and alloxan diabetic rats was investigated. Ten minutes after the administration of this hormone several metabolites (mostly tetrahydrocortisol) and the native hormone were found in liver cytosol, microsomes, mitochondria and nuclei, the relative content of individual compounds in various subcellular fractions being different. In liver mitochondria, microsomes and nuclei of alloxan diabetic rats the concentration of tetrahydrocortisol was decreased, while that of native hormone was increased as compared to normal animals. It was suggested that such changes found in diabetic animals may be one of the causes of increased sensitivity of transcription and translation processes to glucocorticoids. In kidney cytosol and microsomes of intact rats cortisone and tetrahydrocortisol were found. In diabetic animals, however, the concentration of tetrahydrocortisol increased, while that of cortisone was undetectable.

Minchenko AG, Tronjko ND; Endocrinol Exp 22 (1): 19-28 (1988)


5.7 Biological Half-Life

6-8 hours


... After IV administration, hydrocortisone was eliminated with a total body clearance of 18 L/hr and a half-life of 1.7 hr.

Derendorf H et al; J Clin Pharmacol 31 (5): 473-6 (1991)


5.8 Mechanism of Action

Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.


Following topical application, corticosteroids produce anti-inflammatory, antipruritic, and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor. Corticosteroids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Corticosteroids, especially the fluorinated corticosteroids, have antimitotic activity on cutaneous fibroblasts and the epidermis. /Corticosteroids/

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 3525


Reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited following the intravenous administration of hydrocortisone. This is associated with a parallel decrease in intranuclear NFkappaB, known to modulate inflammatory responses including ROS generation. Plasma levels of interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine produced by TH2 cells, are also increased after hydrocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47(phox) subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and plasma IL-10 levels /were investigated/. p47(phox) subunit protein levels in MNC showed a progressive decrease after hydrocortisone administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a nadir between 2 and 4 hours, and returned to a baseline level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and reverted to the baseline levels at 24 hours. In conclusion, p47(phox) subunit suppression may contribute to the inhibition of ROS generation in MNC after hydrocortisone administration. This suppression occurs in parallel with the suppression of NFkappaB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NFkappaB and an increase in IL-10 may cause the inhibitory modulation on p47(phox) subunit and ROS generation by MNC following hydrocortisone and other glucocorticoids.

Dandona P et al; Metabolism 50 (5): 548-52 (2001)


Ask Us for Pharmaceutical Supplier and Partner
Ask Us, Find A Supplier / Partner
No Commissions, No Strings Attached, Get Connected for FREE

What are you looking for?

How can we help you?

The request can't be empty

Please read our Privacy Policy carefully

You must agree to the privacy policy

The name can't be empty
The company can't be empty.
The email can't be empty Please enter a valid email.
The mobile can't be empty