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Chemistry

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Also known as: 50-35-1, Thalomid, 2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, (+/-)-thalidomide, Contergan, Distaval
Molecular Formula
C13H10N2O4
Molecular Weight
258.23  g/mol
InChI Key
UEJJHQNACJXSKW-UHFFFAOYSA-N
FDA UNII
4Z8R6ORS6L

Thalidomide
A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.
The physiologic effect of thalidomide is by means of Decreased Immunologically Active Molecule Activity.
1 2D Structure

Thalidomide

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
2.1.2 InChI
InChI=1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)
2.1.3 InChI Key
UEJJHQNACJXSKW-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1CC(=O)NC(=O)C1N2C(=O)C3=CC=CC=C3C2=O
2.2 Other Identifiers
2.2.1 UNII
4Z8R6ORS6L
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Sedoval

2. Thalomid

2.3.2 Depositor-Supplied Synonyms

1. 50-35-1

2. Thalomid

3. 2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

4. (+/-)-thalidomide

5. Contergan

6. Distaval

7. Pantosediv

8. Softenon

9. Sedoval

10. Kevadon

11. Corronarobetin

12. Psycholiquid

13. Psychotablets

14. Theophilcholine

15. Algosediv

16. Asmadion

17. Bonbrain

18. Calmorex

19. Ectiluran

20. Enterosediv

21. Gastrinide

22. Glutanon

23. Hippuzon

24. Neosedyn

25. Neosydyn

26. Nerosedyn

27. Neufatin

28. Neurodyn

29. Neurosedin

30. Neurosedym

31. Nevrodyn

32. Noctosediv

33. Polygripan

34. Profarmil

35. Quetimid

36. Quietoplex

37. Sandormin

38. Sedimide

39. Sedisperil

40. Shinnibrol

41. Softenil

42. Talargan

43. Talismol

44. Telargean

45. Tensival

46. Thalinette

47. Valgraine

48. Asmaval

49. Calmore

50. Glupan

51. Grippex

52. Imidene

53. Isomin

54. Nibrol

55. Noxodyn

56. Pangul

57. Sleepan

58. Slipro

59. Talimol

60. Telagan

61. Thalin

62. Valgis

63. Yodomin

64. N-phthaloylglutamimide

65. Sedin

66. Predni-sediv

67. Imida-lab

68. N-phthalylglutamic Acid Imide

69. Poly-giron

70. Sedalis Sedi-lab

71. Shin-naito S

72. Neaufatin

73. Asidon 3

74. Pro-ban M

75. 3-phthalimidoglutarimide

76. Imidan (peyta)

77. Neurosedyn

78. Ulcerfen

79. Alpha-phthalimidoglutarimide

80. K-17

81. Bonbrrin

82. Distaxal

83. Distoval

84. Talidomida

85. Kedavon

86. Thaled

87. (+-)-thalidomide

88. 2,6-dioxo-3-phthalimidopiperidine

89. Nsc-66847

90. Thalidomide Celgene

91. Alpha-n-phthalylglutaramide

92. Celgene

93. Pharmion

94. N-(2,6-dioxo-3-piperidyl)phthalimide

95. Glutarimide, 2-phthalimido-

96. N-phthalyl-glutaminsaeure-imid

97. Alpha-(n-phthalimido)glutarimide

98. K 17

99. .alpha.-phthalimidoglutarimide

100. E-217

101. Myrin

102. 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindoline

103. .alpha.-n-phthalylglutaramide

104. 2-(2,6-dioxopiperidin-3-yl)-1h-isoindole-1,3(2h)-dione

105. 1h-isoindole-1,3(2h)-dione, 2-(2,6-dioxo-3-piperidinyl)-

106. Phthalimide, N-(2,6-dioxo-3-piperidyl)-

107. .alpha.-(n-phthalimido)glutarimide

108. 2-(2,6-dioxo-3-piperidinyl)-1h-isoindole-1,3(2h)-dione

109. Mfcd00153873

110. Chembl468

111. Thalidomide (soluble Form)

112. Nsc-527179

113. 2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione

114. 4z8r6ors6l

115. Enmd 0995

116. Thalomide

117. (+-)-n-(2,6-dioxo-3-piperidyl)phthalimide

118. Chebi:74947

119. 2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1h-isoindole-1,3-dione

120. Nsc66847

121. Pro-bam M

122. N-(2,6-dioxo-3-piperidinyl)phthalimide

123. Ncgc00015989-09

124. Talidomide [dcit]

125. Thalidomidum

126. Sedalis

127. Talidomide

128. Telargan

129. Dsstox_cid_2524

130. (+/-)-n-(2,6-dioxo-3-piperidyl)phthalimide

131. Dsstox_rid_76611

132. Dsstox_gsid_22524

133. Talidomida [inn-spanish]

134. Thalidomidum [inn-latin]

135. Thalidomine Usp26

136. 2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione

137. Synovir

138. Talizer

139. (?)-thalidomide

140. Phthalimide,6-dioxo-3-piperidyl)-

141. Wln: T56 Bvnvj C- Dt6vmvtj

142. Thalomid (tm)

143. Thalomid (tn)

144. Thalidomide Pharmion

145. Thaled (tn)

146. N-phthalyl-glutaminsaeure-imid [german]

147. N-phthalimidoglutamic Acid Imide

148. Hsdb 3586

149. 1h-isoindole-1, 2-(2,6-dioxo-3-piperidinyl)-

150. Sr-01000076184

151. Einecs 200-031-1

152. Unii-4z8r6ors6l

153. Nsc 527179

154. Brn 0030233

155. Talinol

156. Thalidomide (jan/usp/inn)

157. Ai3-50606

158. Ccris 8148

159. Nsc-91729

160. Nsc-91730

161. (y)-thalidomide

162. Thalidomide,(s)

163. Cas-50-35-1

164. Prestwick_463

165. Thalidomide [usan:usp:inn:ban:jan]

166. (a+/-)-thalidomide

167. Thalidomide [mi]

168. (+/-)-2-(2,6-dioxo-3-piperidinyl)-1h-isoindole-1,3(2h)-dione

169. Prestwick0_000192

170. Prestwick1_000192

171. Prestwick2_000192

172. Prestwick3_000192

173. Spectrum2_000707

174. Spectrum3_001715

175. Spectrum4_001087

176. Spectrum5_001791

177. Thalidomide [inn]

178. Thalidomide [jan]

179. (.+/-.)-thalidomide

180. Thalidomide [hsdb]

181. Thalidomide [usan]

182. Upcmld-dp139

183. Thalidomide [vandf]

184. Thalomid (tn) (celgene)

185. Schembl7581

186. Nciopen2_003188

187. Thalidomide [mart.]

188. Lopac0_001224

189. Bspbio_000143

190. Bspbio_001156

191. Bspbio_003330

192. Kbiogr_000496

193. Kbiogr_001474

194. Kbiogr_002322

195. Kbioss_000496

196. Kbioss_002324

197. Thalidomide [usp-rs]

198. Thalidomide [who-dd]

199. 2-(2,6-dioxo-3-piperidyl)isoindoline-1,3-dione

200. Mls000069353

201. Divk1c_000051

202. Spectrum1503607

203. Spbio_000893

204. Spbio_002064

205. Thalidomide [ema Epar]

206. Bpbio1_000159

207. Gtpl7327

208. Dtxsid9022524

209. Schembl15197560

210. Upcmld-dp139:001

211. Hms500c13

212. Kbio1_000051

213. Kbio2_000496

214. Kbio2_002322

215. Kbio2_003064

216. Kbio2_004890

217. Kbio2_005632

218. Kbio2_007458

219. Kbio3_000911

220. Kbio3_000912

221. Kbio3_002550

222. Kbio3_002802

223. Thalidomide [orange Book]

224. Cmap_000022

225. Ninds_000051

226. Bio1_000387

227. Bio1_000876

228. Bio1_001365

229. Bio2_000418

230. Bio2_000898

231. Hms1362j17

232. Hms1568h05

233. Hms1792j17

234. Hms1922e12

235. Hms1990j17

236. Hms2090o05

237. Hms2093g15

238. Hms2095h05

239. Hms2234c07

240. Hms3259c22

241. Hms3263f10

242. Hms3266f13

243. Hms3373e06

244. Hms3373g15

245. Hms3403j17

246. Hms3414f19

247. Hms3654a20

248. Hms3678f19

249. Hms3712h05

250. Hms3884i05

251. Pharmakon1600-01503607

252. Thalidomide [usp Monograph]

253. Bcp19772

254. Nsc91729

255. Nsc91730

256. Tox21_110275

257. Tox21_300580

258. Tox21_501224

259. 1h-isoindole-1,3(2h)-dione, 2-(2,6-dioxo-3-piperidinyl)-, (+-)-

260. Ac-917

261. Bbl023439

262. Bdbm50070114

263. Ccg-39878

264. Nsc527179

265. Nsc758479

266. Stl356025

267. ( Inverted Question Mark)-thalidomide

268. Akos009529198

269. Tox21_110275_1

270. Cs-1084

271. Db01041

272. Lp01224

273. Nc00600

274. Nsc-758479

275. Sdccgsbi-0051191.p004

276. (+/-)-thalidomide, >=98%, Powder

277. Idi1_000051

278. Idi1_002173

279. Ncgc00015989-03

280. Ncgc00015989-04

281. Ncgc00015989-05

282. Ncgc00015989-06

283. Ncgc00015989-07

284. Ncgc00015989-08

285. Ncgc00015989-10

286. Ncgc00015989-11

287. Ncgc00015989-12

288. Ncgc00015989-13

289. Ncgc00015989-14

290. Ncgc00015989-16

291. Ncgc00015989-17

292. Ncgc00015989-29

293. Ncgc00024708-02

294. Ncgc00024708-03

295. Ncgc00024708-04

296. Ncgc00024708-05

297. Ncgc00024708-06

298. Ncgc00024708-07

299. Ncgc00024708-08

300. Ncgc00024708-09

301. Ncgc00024708-10

302. Ncgc00024708-11

303. Ncgc00254343-01

304. Ncgc00261909-01

305. 1012310-87-0

306. As-12367

307. Bp-30256

308. Bt164465

309. Hy-14658

310. Nci60_023904

311. Smr000058524

312. Sy052614

313. Wln: T56 Bvnvj C- Dt6vmvtj -d

314. Wln: T56 Bvnvj C- Dt6vmvtj -l

315. Sbi-0051191.p003

316. Db-051759

317. Phthalimide,6-dioxo-3-piperidyl)-, (+)-

318. Phthalimide,6-dioxo-3-piperidyl)-, (-)-

319. Ab00052362

320. Eu-0101224

321. Ft-0600001

322. Ft-0602275

323. Ft-0631211

324. Ft-0675130

325. S1193

326. Sw196678-4

327. T2524

328. Isopropyl (3,4-dichlorophenyl)carbamodithioate

329. Phthalimide,6-dioxo-3-piperidyl)-, D-(+)-

330. Phthalimide,6-dioxo-3-piperidyl)-, L-(-)-

331. C07910

332. D00754

333. Ab00052362-11

334. Ab00052362-12

335. Ab00052362-13

336. Ab00052362_14

337. Ab00052362_15

338. 153t873

339. Q203174

340. Sr-01000076184-1

341. Sr-01000076184-3

342. Sr-01000076184-5

343. Sr-01000076184-8

344. Thalidomide N-(2,6-dioxopiperidin-3-yl)phthalimide

345. W-105969

346. Brd-a93255169-001-04-4

347. Brd-a93255169-001-06-9

348. Brd-a93255169-001-24-2

349. Z1550675451

350. 1h-isoindole-1, 2-(2,6-dioxo-3-piperidinyl)-, (r)-

351. 1h-isoindole-1, 2-(2,6-dioxo-3-piperidinyl)-, (s)-

352. 2-(2,6-dioxo-3-piperidinyl)-1h-isoindole-1,3(2h)-dione #

353. [(r,s)-2-(2,6-dioxo-3-piperidinyl)-1h-isoindole-1,3(2h)-dione

354. Thalidomide, United States Pharmacopeia (usp) Reference Standard

355. ( Inverted Question Mark)-2-(2,6-dioxo-3-piperidinyl)-1h-isoindole-1,3(2h)-dione

356. 1h-isoindole-1,3(2h)-dione, 2-(2,6-dioxo-3-piperidinyl)-, (+/-)-

357. 2-(6-hydroxy-2-oxo-2,3,4,5-tetrahydropyridin-3-yl)-2,3-dihydro-1h-isoindole-1,3-dione

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 258.23 g/mol
Molecular Formula C13H10N2O4
XLogP30.3
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count4
Rotatable Bond Count1
Exact Mass258.06405680 g/mol
Monoisotopic Mass258.06405680 g/mol
Topological Polar Surface Area83.6 Ų
Heavy Atom Count19
Formal Charge0
Complexity449
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameThalomid
PubMed HealthThalidomide (By mouth)
Drug ClassesAntineoplastic Agent, Leprostatic
Drug LabelTHALOMID, -(N-phthalimido) glutarimide, is an immunomodulatory agent. The empirical formula for thalidomide is C13H10N2O4 and the gram molecular weight is 258.2. The CAS number of thalidomide is 50-35-1....
Active IngredientThalidomide
Dosage FormCapsule
Routeoral; Oral
Strength200mg; 150mg; 100mg; 50mg
Market StatusPrescription
CompanyCelgene

2 of 2  
Drug NameThalomid
PubMed HealthThalidomide (By mouth)
Drug ClassesAntineoplastic Agent, Leprostatic
Drug LabelTHALOMID, -(N-phthalimido) glutarimide, is an immunomodulatory agent. The empirical formula for thalidomide is C13H10N2O4 and the gram molecular weight is 258.2. The CAS number of thalidomide is 50-35-1....
Active IngredientThalidomide
Dosage FormCapsule
Routeoral; Oral
Strength200mg; 150mg; 100mg; 50mg
Market StatusPrescription
CompanyCelgene

4.2 Therapeutic Uses

Angiogenesis Inhibitors; Immunosuppressive Agents; Leprostatic Agents; Teratogens

National Library of Medicine's Medical Subject Headings. Thalidomide. Online file (MeSH, 2014). Available from, as of December 18, 2014: https://www.nlm.nih.gov/mesh/2014/mesh_browser/MBrowser.html


Thalomid in combination with dexamethasone is indicated for the treatment of patients with newly diagnosed multiple myeloma (MM). /Included in US product label/

NIH; DailyMed. Current Medication Information for Thalomid (Thalidomide) Capsule (Updated: June 2014). Available from, as of February 9, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2eda833b-1357-4ed4-a093-194524fcb061


Thalomid is indicated for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). /Included in US product label/

NIH; DailyMed. Current Medication Information for Thalomid (Thalidomide) Capsule (Updated: June 2014). Available from, as of February 9, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2eda833b-1357-4ed4-a093-194524fcb061


Thalomid is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of erythema nodosum leprosum (ENL) recurrence. /Included in US product label/

NIH; DailyMed. Current Medication Information for Thalomid (Thalidomide) Capsule (Updated: June 2014). Available from, as of February 9, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2eda833b-1357-4ed4-a093-194524fcb061


For more Therapeutic Uses (Complete) data for THALIDOMIDE (17 total), please visit the HSDB record page.


4.3 Drug Warning

/BOXED WARNING/ WARNING: EMBRYO-FETAL TOXICITY. If thalidomide is taken during pregnancy, it can cause severe birth defects or embryo-fetal death. Thalidomide should never be used by females who are pregnant or who could become pregnant while taking the drug. Even a single dose (1 capsule (regardless of strength)) taken by a pregnant woman during her pregnancy can cause severe birth defects. Because of this toxicity and in an effort to make the chance of embryo-fetal exposure to Thalomid (thalidomide) as negligible as possible, Thalomid (thalidomide) is approved for marketing only through a special restricted distribution program: Thalomid REMS program, approved by the Food and Drug Administration. This program was formerly known as the "System for Thalidomide Education and Prescribing Safety (S.T.E.P.S. program)".

NIH; DailyMed. Current Medication Information for Thalomid (Thalidomide) Capsule (Updated: June 2014). Available from, as of February 9, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2eda833b-1357-4ed4-a093-194524fcb061


/BOXED WARNING/ WARNING: VENOUS THROMBOEMBOLISM. The use of Thalomid (thalidomide) in multiple myeloma results in an increased risk of venous thromboembolism, such as deep venous thrombosis and pulmonary embolism. This risk increases significantly when thalidomide is used in combination with standard chemotherapeutic agents including dexamethasone. In one controlled trial, the rate of venous thromboembolism was 22.5% in patients receiving thalidomide in combination with dexamethasone compared to 4.9% in patients receiving dexamethasone alone (p = 0.002). Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Instruct patients to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Consider thromboprophylaxis based on an assessment of individual patients' underlying risk factors.

NIH; DailyMed. Current Medication Information for Thalomid (Thalidomide) Capsule (Updated: June 2014). Available from, as of February 9, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2eda833b-1357-4ed4-a093-194524fcb061


Use of thalidomide in patients with multiple myeloma is associated with increased risk of venous thromboembolic events (e.g., deep venous thrombosis, pulmonary embolus). Such risk increases substantially when thalidomide is used in combination with standard chemotherapy, including dexamethasone. In a controlled clinical trial, an increased incidence of venous thromboembolic events was observed in patients receiving thalidomide in combination with dexamethasone compared with those receiving dexamethasone alone (22.5 versus 4.9%). Patients and clinicians are advised to watch for signs and symptoms of thromboembolism. Patients should be instructed to notify a clinician if they develop shortness of breath, chest pain, and/or arm or leg swelling.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 3646


Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common (> or =10%) and potentially severe adverse reaction of treatment with thalidomide that may be irreversible. Peripheral neuropathy generally occurs following chronic use over a period of months; however, peripheral neuropathy following relatively short-term use has been reported. The correlation with cumulative dose is unclear. Symptoms may occur some time after thalidomide treatment has been stopped and may resolve slowly or not at all.

NIH; DailyMed. Current Medication Information for Thalomid (Thalidomide) Capsule (Updated: June 2014). Available from, as of February 9, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2eda833b-1357-4ed4-a093-194524fcb061


For more Drug Warnings (Complete) data for THALIDOMIDE (36 total), please visit the HSDB record page.


4.4 Drug Indication

For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Also for use as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.


FDA Label


Thalidomide BMS in combination with melphalan and prednisone as first line treatment of patients with untreated multiple myeloma, aged > /= 65 years or ineligible for high dose chemotherapy.

Thalidomide BMS is prescribed and dispensed according to the Thalidomide Celgene Pregnancy Prevention Programme (see section 4. 4).


Thalidomide Lipomed in combination with melphalan and prednisone is indicated as first line treatment of patients with untreated multiple myeloma, aged 65 years or ineligible for high dose chemotherapy.

Thalidomide Lipomed is prescribed and dispensed in accordance with the Thalidomide Lipomed Pregnancy Prevention Programme (see section 4. 4).


5 Pharmacology and Biochemistry
5.1 Pharmacology

Thalidomide is an immunomodulatory agent with a spectrum of activity that is not fully characterized. Thalidomide is racemic — it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. The enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.


5.2 MeSH Pharmacological Classification

Teratogens

An agent that causes the production of physical defects in the developing embryo. (See all compounds classified as Teratogens.)


Immunosuppressive Agents

Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. (See all compounds classified as Immunosuppressive Agents.)


Leprostatic Agents

Substances that suppress Mycobacterium leprae, ameliorate the clinical manifestations of leprosy, and/or reduce the incidence and severity of leprous reactions. (See all compounds classified as Leprostatic Agents.)


Angiogenesis Inhibitors

Agents and endogenous substances that antagonize or inhibit the development of new blood vessels. (See all compounds classified as Angiogenesis Inhibitors.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
THALIDOMIDE
5.3.2 FDA UNII
4Z8R6ORS6L
5.3.3 Pharmacological Classes
Decreased Immunologically Active Molecule Activity [PE]
5.4 ATC Code

L04AX02


L04AX02


L04AX02

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


L - Antineoplastic and immunomodulating agents

L04 - Immunosuppressants

L04A - Immunosuppressants

L04AX - Other immunosuppressants

L04AX02 - Thalidomide


5.5 Absorption, Distribution and Excretion

Absorption

The absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. In studies of both healthy volunteers and subjects with Hansen’s disease, the mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours indicating that thalidomide is slowly absorbed from the gastrointestinal tract.


Route of Elimination

Thalidomide itself has less than 0.7% of the dose excreted in the urine as unchanged drug.


... Thalidomide given orally to rats was poorly absorbed.

Hayes, W.J., Jr., E.R. Laws Jr., (eds.). Handbook of Pesticide Toxicology Volume 1. General Principles. New York, NY: Academic Press, Inc., 1991., p. 76


In animal studies, high concentrations of thalidomide were found in the gastrointestinal tract, liver, and kidney; and lower concentrations were found in the muscle, brain, and adipose tissue. Thalidomide crosses the placenta. It is not known whether thalidomide is present in the ejaculate of males.

USP. Convention. USPDI - Drug Information for the Health Care Professional. 19th ed. Volume I.Micromedex, Inc. Englewood, CO., 1999. Content Prepared by the U.S. Pharmacopieal Convention, Inc., p. 2778


Thalidomide has a renal clearance of 1.15 mL per minute; less than 0.7% of the total dose is excreted unchanged.

USP. Convention. USPDI - Drug Information for the Health Care Professional. 19th ed. Volume I.Micromedex, Inc. Englewood, CO., 1999. Content Prepared by the U.S. Pharmacopieal Convention, Inc., p. 2778


... The present study determined the bioequivalence and pharmacokinetics of ... commercial and clinical trial thalidomide formulations and the Brazillian Tortuga formulation in an open label, single dose, three-way crossover design. ... The terminal rate constant for the Tortuga formulation was significantly less, giving rise to a terminal half-life of 15 hr compared to about 5-6 hr in the /Commercial/ formulations. ... Extent of absorption, as measured by AUC0-infinity was approx equal for all three formulations. Terminal half-life for Tortuga was two to three times longer than compared to the /commercial/ formulations and is clear evidence for absorption rate limitations. The two ... /commercial/ formulations showed similar pharmacokinetic parameters with profiles that were best described by one compartment model with first order absorption and elimination. ...

Teo SK, et al; J Clin Pharm 39 (11): 1162-8 (1999)


For more Absorption, Distribution and Excretion (Complete) data for THALIDOMIDE (20 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Thalidomide itself does not appear to be hepatically metabolized to any large extent, but appears to undergo non-enzymatic hydrolysis in plasma to multiple metabolites. Thalidomide may be metabolized hepatically by enzymes of the cytochrome P450 enzyme system. The end product of metabolism, phthalic acid, is excreted as a glycine conjugate.


Studies on thalidomide metabolism in humans have not been done. In animals, nonenzymatic hydrolytic cleavage appears to be the main pathway of degradation, producing seven major and at least five minor hydrolysis products. Thalidomide may be metabolized hepatically by the enzymes of the cytochrome p450 enzyme system. Thalidomide does not appear to induce or inhibit its own metabolism. However, it may interfere with enzyme induction caused by other compounds. The end product of metabolism, phthalic acid, is excreted as a glycine conjugate.

USP. Convention. USPDI - Drug Information for the Health Care Professional. 19th ed. Volume I.Micromedex, Inc. Englewood, CO., 1999. Content Prepared by the U.S. Pharmacopieal Convention, Inc., p. 2778


The chiral inversion and hydrolysis of thalidomide and the catalysis by bases and human serum albumin were investigated by /utilizing/ a stereoselective HPLC assay. Chiral inversion was catalyzed by albumin, hydroxyl ions, phosphate and amino acids. Basic amino acids (arginine and lysine) had a superior potency in catalyzing chiral inversion compared to acid and neutral ones. The chiral inversion of thalidomide is thus subject to specific and general base catalysis and it is suggested that the ability of HSA to catalyze the reaction is due to basic groups of the amino acids arginine and lysine and not to a single catalytic site on the macromolecule. The hydrolysis of thalidomide was also base catalyzed. ... Albumin had no effect on hydrolysis and there was no difference between the catalytic potencies of acidic, neutral and base amino acids. ... Chiral inversion is deduced to occur by electrophilic substitution involving specific and general base catalysis, whereas hydrolysis is thought to occur by nucleophilic substitution involving specific and general base as well as nucleophilic catalysis. As nucleophilic attack is sensitive to steric properties of the catalyst, steric hindrance might be the reason albumin is not able to catalyze hydrolysis. (1)H NMR experiments revealed that the three teratogenic metabolites of thalidomide, in sharp contrast to the drug itself had complete chiral stability. This leads to the speculation that, were some enantioselectivity to exist in the teratogenicity of thalidomide, it could result from fast hydrolysis to chirally stable teratogenic metabolites.

PMID:9860497 Reist M, et al; Chem Res Toxicol 11 (12): 1521-8 (1998)


Thalidomide has been shown to be an inhibitor of angiogenesis in a rabbit cornea micropocket model; however, it has failed to demonstrate this activity in other models. These results suggest that the anti-angiogenic effects of thalidomide may only be observed following metabolic activation of the compound. This activation process may be species specific, similar to the teratogenic properties associated with thalidomide. Using a rat aorta model and human aortic endothelial cells, we co-incubated thalidomide in the presence of either human, rabbit, or rat liver microsomes. These experiments demonstrated that thalidomide inhibited microvessel formation from rat aortas and slowed human aortic endothelial cell proliferation in the presence of human or rabbit microsomes, but not in the presence of rat microsomes. In the absence of microsomes, thalidomide had no effect on either microvessel formation or cell proliferation, thus demonstrating that a metabolite of thalidomide is responsible for its anti-angiogenic effects and that this metabolite can be formed in both humans and rabbits, but not in rodents. /There are five primary metabolites of thalidomide [4-OH-thalidomide, 3-OH-thalidomide, 39-OH-thalidomide, 49-OH-thalidomide, and 59-OH-thalidomide], and the antiangiogenic property could be the result of either of these compounds, or of an intermediate. Also, thalidomide undergoes rapid spontaneous hydrolysis in aqueous solutions at a pH of 6.0 or greater to form three primary products [4-phthalimidoglutaramic acid, 2-phthalimidoglutaramic acid, and a-(o-carboxybenzamido) glutarimide] and eight minor products. Furthermore, each of the five metabolites of the parent compound undergoes similar hydrolysis./

PMID:9714301 Bauer KS, et al; Biochem Pharmacol 55 (11): 1827-34 (1998)


Three CD-1 mice were dosed orally with 3000 mg/kg thalidomide in 1% carboxymethylcellulose daily for three days and plasma samples were obtained 2, 4 and 6 hours postdose on the third day. Extracts of mouse plasma from thalidomide treated mice contained at least four components that absorbed at 230 nm, not observed in control plasma extracts. The first two components did not match any standards and may represent other metabolites, possibly hydrolysis products of thalidomide. The second pair of components closely matched standards for 4-hydroxythhalidomide and thalidomide respectively.

European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP), European Public Assessment Report (EPAR): Thalidomide Pharmion (Thalidomide) p.10 (2008). Available from, as of February 10, 2015: https://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000823/WC500037054.pdf


For more Metabolism/Metabolites (Complete) data for THALIDOMIDE (7 total), please visit the HSDB record page.


5.7 Biological Half-Life

The mean half-life of elimination ranges from approximately 5 to 7 hours following a single dose and is not altered upon multiple dosing.


... The pharmacokinetics and hemodynamic effects of two oral doses of thalidomide (100 and 200 mg) were investigated, using a randomized two period crossover design, in a group of asymptomatic male HIV seropositive subjects. Thalidomide pharmacokinetics were linear at the doses studied, and were best described by a one compartment model with first order absorption and elimination processes. The drug was rapidly absorbed with a mean absorption half life of 0.95 hr (range 0.16-2.49 hr) and 1.19 hr (0.33-3.53 hr) after 100 and 200 mg doses, respectively. The corresponding Cmax values were 1.15 +/-0.24 ug/mL (100 mg) and 1.92 +/- 0.47- ug/mL (200 mg; p<0.001) which were achieved (Tmax) at 2.5 +/-1.5 hr and 3.3 +/-1.4 hr, respectively. Plasma concn of thalidomide declined thereafter, in a log linear manner, with elimination half lives of 4.6+/-1.2 hr (100 mg) and 5.3+/-2.2 hr -(200 mg). The apparent volumes of distribution (Vdss/F) were 69.9+/-1.56 L (100 mg) and 82.7+/-34.9 L (200 mg) while total body clearances (C1F) were 10.4+/-2.1 and 10.8+/- 1.7 L/hr, respectively. ...

Noormohamed FH, et al; Airs Res Human Retroviruses 15 (12): 1047-52 (1999)


The mean elimination half-life of thalidomide following a single 200-mg oral dose ranges from 3-6.7 hours and the elimination half-life appears to be similar following multiple doses of the drug. In a study in healthy adults who received a single 50-, 200-, or 400-mg oral dose of the drug, the mean elimination half-life of thalidomide was 5.5, 5.5, or 7.3 hours, respectively. The mean elimination half-life of thalidomide was 6.9 hours in adults with leprosy who received a single 400-mg oral dose and 4.6-6.5 hours in HIV-infected adults who received a single 100- to 300-mg dose.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 3653


5.8 Mechanism of Action

In patients with erythema nodosum leprosum (ENL) the mechanism of action is not fully understood. Available data from in vitro studies and preliminary clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-a) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-a in patients with ENL, however, it has also been shown to increase plasma TNF-a levels in HIV-seropositive patients. As a cancer treatment, the drug may act as a VEGF inhibitor.


The sedative drug thalidomide ([+]-alpha-phthalimidoglutarimide), once abandoned for causing birth defects in humans, has found new therapeutic license in leprosy and other diseases, with renewed teratological consequences. Although the mechanism of teratogenesis and determinants of risk remain unclear, related teratogenic xenobiotics are bioactivated by embryonic prostaglandin H synthase (PHS) to a free-radical intermediates that produce reactive oxygen species (ROS), which cause oxidative damage to DNA and other cellular macromolecules. Similarly, thalidomide is bioactivated by horseradish peroxidase, and oxidizes DNA and glutathione, indicating free radical-mediated oxidative stress. Furthermore, thalidomide teratogenicity in rabbits is reduced by the PHS inhibitor acetylsalicylic acid, indicating PHS-catalyzed bioac