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Technical details about Triamterene, learn more about the structure, uses, toxicity, action, side effects and more

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2D Structure
Also known as: 396-01-0, 6-phenylpteridine-2,4,7-triamine, 2,4,7-triamino-6-phenylpteridine, Dyrenium, Dytac, Pterofen
Molecular Formula
C12H11N7
Molecular Weight
253.26  g/mol
InChI Key
FNYLWPVRPXGIIP-UHFFFAOYSA-N
FDA UNII
WS821Z52LQ

A pteridinetriamine compound that inhibits SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS.
Triamterene is a Potassium-sparing Diuretic. The physiologic effect of triamterene is by means of Decreased Renal K+ Excretion, and Increased Diuresis.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
6-phenylpteridine-2,4,7-triamine
2.1.2 InChI
InChI=1S/C12H11N7/c13-9-7(6-4-2-1-3-5-6)16-8-10(14)18-12(15)19-11(8)17-9/h1-5H,(H6,13,14,15,17,18,19)
2.1.3 InChI Key
FNYLWPVRPXGIIP-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1=CC=C(C=C1)C2=NC3=C(N=C(N=C3N=C2N)N)N
2.2 Other Identifiers
2.2.1 UNII
WS821Z52LQ
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Dyrenium

2. Dytac

3. Urocaudal

2.3.2 Depositor-Supplied Synonyms

1. 396-01-0

2. 6-phenylpteridine-2,4,7-triamine

3. 2,4,7-triamino-6-phenylpteridine

4. Dyrenium

5. Dytac

6. Pterofen

7. Pterophene

8. Triamteren

9. Triamteril

10. Triteren

11. Ademin

12. Ademine

13. Diurene

14. Noridil

15. Taturil

16. Teridin

17. Urocaudal

18. Jatropur

19. Noridyl

20. Triampur

21. Diren

22. Ditak

23. Dyren

24. Teriam

25. Tri-span

26. Triamteril Complex

27. Trispan

28. 6-phenyl-2,4,7-pteridinetriamine

29. 2,4,7-pteridinetriamine, 6-phenyl-

30. Sk&f 8542

31. 6-phenyl-2,4,7-triaminopteridine

32. Skf 8542

33. Pteridine, 2,4,7-triamino-6-phenyl-

34. 2,4,7-triamino-6-fenilpteridina

35. Nsc 77625

36. Nsc-77625

37. Sk-8542

38. Brn 0266723

39. Diucelpin

40. Sk&f-8542

41. Ws821z52lq

42. Masuharmin

43. Triamizide

44. Triamthiazid

45. Amteren

46. Dinazide

47. Diutensat

48. Diuteren

49. Dyberzide

50. Dytenzide

51. Esiteren

52. Hidiurese

53. Hydrene

54. Hypertorr

55. Jenateren

56. Kalspare

57. Nephral

58. Renezide

59. Reviten

60. Tricilone

61. Triurene

62. Uretren

63. Diarol

64. Isobar

65. Trizid

66. Anjal

67. Dazid

68. Turfa

69. Apo-triazide

70. Thiazid Wolff

71. Nci-c56042

72. Nsc77625

73. Ademin(e)

74. Nsc-639359

75. Ncgc00016016-10

76. Triamterena

77. Triamterenum

78. Cas-396-01-0

79. Triazide

80. Fluss 40

81. Sali-puren

82. Dsstox_cid_1373

83. Dsstox_rid_76117

84. Dsstox_gsid_21373

85. Triamterenum [inn-latin]

86. Triamterena [inn-spanish]

87. Dyrenium (tn)

88. Ccris 5872

89. Pteridine Deriv. 11

90. Hsdb 3405

91. 2,4,7-triamino-6-fenilpteridina [italian]

92. Nci C56042

93. Sr-01000002968

94. Einecs 206-904-3

95. Nsc 639359

96. Unii-ws821z52lq

97. Ai3-60017

98. Prestwick_480

99. Mfcd00006708

100. Dyazide (salt/mix)

101. Triamterene [usan:usp:inn:ban:jan]

102. Spectrum_000508

103. Triamterene, >=99%

104. Triamterene [mi]

105. Prestwick0_000034

106. Prestwick1_000034

107. Prestwick2_000034

108. Prestwick3_000034

109. Spectrum2_000938

110. Spectrum3_001372

111. Spectrum4_000366

112. Spectrum5_001034

113. Lopac-t-4143

114. Triamterene [inn]

115. Triamterene [jan]

116. Triamterene [hsdb]

117. Triamterene [iarc]

118. Triamterene [usan]

119. Chembl585

120. T 4143

121. Triamterene [vandf]

122. Nciopen2_004741

123. Triamterene [mart.]

124. Lopac0_001196

125. Oprea1_825704

126. Schembl40707

127. Bspbio_000127

128. Bspbio_002924

129. Kbiogr_000831

130. Kbioss_000988

131. Triamterene [usp-rs]

132. Triamterene [who-dd]

133. 5-26-17-00447 (beilstein Handbook Reference)

134. Mls000069431

135. Bidd:gt0534

136. Divk1c_000433

137. Spectrum1500589

138. Spbio_000876

139. Spbio_002048

140. Bdbm6644

141. Bpbio1_000141

142. Chebi:9671

143. Gtpl4329

144. Triamterene (jp17/usp/inn)

145. 2,7-triamino-6-phenylpteridine

146. 6-phenyl-2,7-triaminopteridine

147. Dtxsid6021373

148. Hms501f15

149. Kbio1_000433

150. Kbio2_000988

151. Kbio2_003556

152. Kbio2_006124

153. Kbio3_002144

154. Skf8542

155. Triamterene [orange Book]

156. Ninds_000433

157. Hms1568g09

158. Hms2092o17

159. Hms2095g09

160. Hms2232b04

161. Hms3259c08

162. Hms3263p13

163. Hms3371d10

164. Hms3652e10

165. Hms3712g09

166. Pharmakon1600-01500589

167. Triamterene [ep Monograph]

168. Triamterene [usp Impurity]

169. Zinc120286

170. 2,7-pteridinetriamine, 6-phenyl-

171. Pteridine,4,7-triamino-6-phenyl-

172. Triamterene [usp Monograph]

173. Bcp28855

174. Dyazide Component Triamterene

175. Hy-b0575

176. Maxzide Component Triamterene

177. Tox21_110283

178. Tox21_202021

179. Tox21_302833

180. Tox21_501196

181. Ccg-40090

182. Nsc639359

183. Nsc757367

184. S4080

185. Stk300348

186. Akos003790819

187. Tox21_110283_1

188. Db00384

189. Lp01196

190. Nc00544

191. Nsc-757367

192. Sdccgsbi-0051163.p004

193. Triamterene Component Of Dyazide

194. Triamterene Component Of Maxzide

195. Idi1_000433

196. Smp1_000147

197. Ncgc00016016-01

198. Ncgc00016016-02

199. Ncgc00016016-03

200. Ncgc00016016-04

201. Ncgc00016016-05

202. Ncgc00016016-06

203. Ncgc00016016-07

204. Ncgc00016016-08

205. Ncgc00016016-09

206. Ncgc00016016-11

207. Ncgc00016016-12

208. Ncgc00016016-13

209. Ncgc00016016-14

210. Ncgc00016016-15

211. Ncgc00016016-16

212. Ncgc00016016-18

213. Ncgc00016016-28

214. Ncgc00016016-29

215. Ncgc00023458-03

216. Ncgc00023458-04

217. Ncgc00023458-05

218. Ncgc00023458-06

219. Ncgc00023458-07

220. Ncgc00256495-01

221. Ncgc00259570-01

222. Ncgc00261881-01

223. Ac-14066

224. As-12471

225. Smr000059118

226. Sbi-0051163.p003

227. Db-049442

228. Ab00052116

229. B2275

230. Bb 0256885

231. Eu-0101196

232. Sw196688-3

233. T1288

234. Triamterene 1.0 Mg/ml In Dimethyl Sulfoxide

235. D00386

236. D95706

237. Wln: T66 Bn Dn Gn Jnj Cz Ez Hr& Iz

238. Ab00052116_13

239. Ab00052116_14

240. 396t010

241. A824641

242. Q221520

243. Sr-01000002968-2

244. Sr-01000002968-4

245. Sr-01000002968-6

246. Brd-k92049597-001-05-9

247. Brd-k92049597-001-10-9

248. Z275128596

249. Triamterene, British Pharmacopoeia (bp) Reference Standard

250. Triamterene, European Pharmacopoeia (ep) Reference Standard

251. Triamterene, United States Pharmacopeia (usp) Reference Standard

252. Triamterene, Pharmaceutical Secondary Standard; Certified Reference Material

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 253.26 g/mol
Molecular Formula C12H11N7
XLogP31
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count7
Rotatable Bond Count1
Exact Mass253.10759338 g/mol
Monoisotopic Mass253.10759338 g/mol
Topological Polar Surface Area130 Ų
Heavy Atom Count19
Formal Charge0
Complexity307
Isotope Atom Count0
Defined Atom Stereocenter Count0
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 2  
Drug NameDyrenium
PubMed HealthTriamterene (By mouth)
Drug ClassesCardiovascular Agent
Drug LabelEach capsule for oral use, with opaque red cap and body, contains Triamterene USP, 50 or 100 mg, and is imprinted with the product name, DYRENIUM, strength (50 mg or 100 mg) and WPC 002 (for the 50-mg strength) and WPC 003 (for the 100-mg strength)....
Active IngredientTriamterene
Dosage FormCapsule
RouteOral
Strength100mg; 50mg
Market StatusPrescription
CompanyWellspring Pharm

2 of 2  
Drug NameDyrenium
PubMed HealthTriamterene (By mouth)
Drug ClassesCardiovascular Agent
Drug LabelEach capsule for oral use, with opaque red cap and body, contains Triamterene USP, 50 or 100 mg, and is imprinted with the product name, DYRENIUM, strength (50 mg or 100 mg) and WPC 002 (for the 50-mg strength) and WPC 003 (for the 100-mg strength)....
Active IngredientTriamterene
Dosage FormCapsule
RouteOral
Strength100mg; 50mg
Market StatusPrescription
CompanyWellspring Pharm

4.2 Therapeutic Uses

Diuretics; Epithelial Sodium Channel Blockers

National Library of Medicine's Medical Subject Headings. Triamterene. Online file (MeSH, 2018). Available from, as of August 29, 2018: https://meshb.nlm.nih.gov/search


/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Triamterene is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of August 29, 2018: https://clinicaltrials.gov/


Dyrenium (triamterene) is indicated in the treatment of edema associated with congestive heart failure, cirrhosis of the liver and the nephrotic syndrome; steroid-induced edema, idiopathic edema and edema due to secondary hyperaldosteronism. /Included in US product labeling/

NIH; DailyMed. Current Medication Information for Dyrenium (Triamterene Capsule) (Updated: August 7, 2017). Available from, as of November 27, 2018: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebb177c0-d45d-4443-a85a-e76bd9931a42


Dyrenium may be used alone or with other diuretics, either for its added diuretic effect or its potassium-sparing potential. It also promotes increased diuresis when patients prove resistant or only partially responsive to thiazides or other diuretics because of secondary hyperaldosteronism. /Included in US product labeling/

NIH; DailyMed. Current Medication Information for Dyrenium (Triamterene Capsule) (Updated: August 7, 2017). Available from, as of November 27, 2018: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebb177c0-d45d-4443-a85a-e76bd9931a42


For more Therapeutic Uses (Complete) data for Triamterene (6 total), please visit the HSDB record page.


4.3 Drug Warning

/BOXED WARNING/ Warnings: Abnormal elevation of serum potassium levels (greater than or equal to 5.5 mEq/liter) can occur with all potassium-sparing agents, including Dyrenium. Hyperkalemia is more likely to occur in patients with renal impairment and diabetes (even without evidence of renal impairment), and in the elderly or severely ill. Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals especially in patients receiving Dyrenium, when dosages are changed or with any illness that may influence renal function.

NIH; DailyMed. Current Medication Information for Dyrenium (Triamterene Capsule) (Updated: August 7, 2017). Available from, as of November 27, 2018: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebb177c0-d45d-4443-a85a-e76bd9931a42


Dyrenium should not be given to patients receiving other potassium-sparing agents, such as spironolactone, amiloride hydrochloride, or other formulations containing triamterene. Two deaths have been reported in patients receiving concomitant spironolactone and Dyrenium or Dyazide. Although dosage recommendations were exceeded in one case and in the other serum electrolytes were not properly monitored, these two drugs should not be given concomitantly.

NIH; DailyMed. Current Medication Information for Dyrenium (Triamterene Capsule) (Updated: August 7, 2017). Available from, as of November 27, 2018: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebb177c0-d45d-4443-a85a-e76bd9931a42


Dyrenium (triamterene) should not be used in patients with pre-existing elevated serum potassium, as is sometimes seen in patients with impaired renal function or azotemia, or in patients who develop hyperkalemia while on the drug. Patients should not be placed on dietary potassium supplements, potassium salts or potassium-containing salt substitutes in conjunction with Dyrenium.

NIH; DailyMed. Current Medication Information for Dyrenium (Triamterene Capsule) (Updated: August 7, 2017). Available from, as of November 27, 2018: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebb177c0-d45d-4443-a85a-e76bd9931a42


Potassium loss has been reported during triamterene therapy in some patients with hepatic cirrhosis and may result in signs and symptoms of hepatic coma or precoma. Serum potassium concentrations should be closely monitored in patients with hepatic cirrhosis and potassium supplementation administered if required.

American Society of Health-System Pharmacists; Drug Information 2018. Bethesda, MD. 2018, p. 2877


For more Drug Warnings (Complete) data for Triamterene (25 total), please visit the HSDB record page.


4.4 Drug Indication

Triamterene is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and the nephrotic syndrome; also in steroid-induced edema, idiopathic edema, and edema due to secondary hyperaldosteronism. Triamterene in combination with hydrochlorothiazide is indicated for the managment of hypertension or treatment of edema in patients who develop hypokalemia following hydrochlorothiazide monotherapy, and in patients who require thiazide diuretic and in whom the development of hypokalemia cannot be risked. Triamterene allows the maintenance of potassium balance when given in combination with loop diuretics and thiazides.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypertension and edema. It primarily works on the distal nephron in the kidneys; it acts from the late distal tubule to the collecting duct to inhibit Na+ reabsorption and decreasing K+ excretion. As triamterene tends to conserve potassium more strongly than promoting Na+ excretion, it can cause an increase in serum potassium, which may result in hyperkalemia potentially associated with cardiac irregularities. In healthy volunteers administered with oral triamterene, there was an increase in the renal clearnace of sodium and magnesium, and a decrease in the clearance of uric acid and creatinine due to its effect of reducing glomerular filtration renal plasma flow. Triamterene does not affect calcium excretion. In clinical trials, the use of triamterene in combination with hydrochlorothiazide resulted an enhanced blood pressure-lowering effects of hydrochlorothiazide.


5.2 MeSH Pharmacological Classification

Diuretics

Agents that promote the excretion of urine through their effects on kidney function. (See all compounds classified as Diuretics.)


Epithelial Sodium Channel Blockers

A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS. (See all compounds classified as Epithelial Sodium Channel Blockers.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
TRIAMTERENE
5.3.2 FDA UNII
WS821Z52LQ
5.3.3 Pharmacological Classes
Increased Diuresis [PE]; Potassium-sparing Diuretic [EPC]; Decreased Renal K+ Excretion [PE]
5.4 ATC Code

C - Cardiovascular system

C03 - Diuretics

C03D - Aldosterone antagonists and other potassium-sparing agents

C03DB - Other potassium-sparing agents

C03DB02 - Triamterene


5.5 Absorption, Distribution and Excretion

Absorption

Triamterene is shown to be rapidly absorbed in the gastrointestinal tract Its onset of action achiveved within 2 to 4 hours after oral ingestion and its duration of action is 12-16 hours. It is reported that the diuretic effect of triamterene may not be observed for several days after administration. In a pharmacokinetic study, the oral bioavailability of triamterene was determined to be 52%. Following administration of a single oral dose to fasted healthy male volunteers, the mean AUC of triamterene was about 148.7 ng*hr/mL and the mean peak plasma concentrations (Cmax) were 46.4 ng/mL reached at 1.1 hour after administration. In a limited study, administration of triamterene in combination with hydrochlorothiazide resulted in an increased bioavailability of triamterene by about 67% and a delay of up to 2 hours in the absorption of the drug. It is advised that triamterene is administered after meals; in a limited study, combination use of triamterene and hydrochlorothiazide with the consumption of a high-fat meal resulted in an increase in the mean bioavailability and peak serum concentrations of triamterene and its active sulfate metabolite, as well as a delay of up to 2 hours in the absorption of the active constituents.


Route of Elimination

Triamterene and its metabolites are excreted by the kidney by filtration and tubular secretion. Upon oral ingestion, somewhat less than 50% of the oral dose reaches the urine. About 20% of an oral dose appears unchanged in the urine, 70% as the sulphate ester of hydroxytriamterene and 10% as free hydroxytriamterene and triamterene glucuronide.


Volume of Distribution

In a pharmacolinetic study involving healthy volunteers receiving triamterene intravenously, the volumes of distribution of the central compartment of triamterene and its hydroxylated ester metabolite were 1.49 L/kg and 0.11 L/kg, respectively. Triamterene was found to cross the placental barrier and appear in the cord blood of animals.


Clearance

The total plasma clearance was 4.5 l/min and renal plasma clearance was 0.22 l/kg following intravenous administration of triamterene in healthy volunteers.


Earlier in vivo studies revealed a low concentration of triamterene in the brain of guinea pigs and baboons, and a transfer of the drug from the fetus to the mother. Additional investigations have been performed to characterize further the transport system(s) for triamterene in the central nervous system (CNS), placenta, and kidney. In guinea pigs a very low brain to free plasma concentration ratio (0.1) was achieved 3.5 min after drug administration and was maintained during 180 min of drug infusion. The cerebrospinal fluid (CSF) concentration was similar to the concentration of the drug in the brain. A higher brain to free plasma concentration ratio was gradually reached in dogs studied with nanogram per ml and microgram per ml concentrations of triamterene in CSF. Administration of triamterene to fetal and maternal sheep revealed a placental extraction (E) from fetal plasma to placenta 20 times greater than that from maternal plasma to placenta. The E from fetal plasma to placenta was unaffected by a triamterene concentration in the maternal circulation 10 times that in the fetus. These findings and studies of renal clearance support an active transfer of triamterene by the CNS, placenta, and kidney; the physiologic substrate for these systems is unknown.

PMID:234832 Pruitt AW et al; Drug Metab Dispos 3 (1): 30-41 (1975)


The kinetics of triamterene and its active phase II metabolite were studied in 32 patients with various degrees of impaired renal function; the creatinine clearances ranged from 135 to 10 mL/min. The area under the plasma concentration-time curves (AUC) for triamterene were not influenced by kidney function, but the AUCs for the effective metabolite OH-TA-ester were significantly elevated in renal failure, indicating accumulation of the metabolite. Urinary recovery of triamterene and its metabolite over a 48 hr collection period was significantly reduced in renal failure. This is considered to be due to delayed urinary excretion, corresponding to reduced renal clearance. The renal clearance of the native drug exceeded that of the metabolite, because of their different protein binding, 55% for triamterene and 91% for the metabolite. The latter is eliminated almost exclusively via tubular secretion and extra-renal elimination is less important. ...

PMID:6861860 Knauf H et al; Eur J Clin Pharmacol 24 (4): 453-6 (1983)


Although renal elimination is only a minor route of excretion for triamterene, it is the main route of elimination of 4'-hydroxytriamterene sulfate. Thus, in individuals with renal impairment, accumulation of the sulfate is substantial and progressive, but negligible for triamterene. The kinetics of triamterene were observed in 32 patients with widely varying degrees of creatinine clearance (10-135 mL/minute), an indicator of renal function. In patients with reduced renal function, significant accumulation in plasma and reduced renal clearance of the sulfate were reported. Plasma concentrations of the parent drug were not increased.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V108 278 (2016)


Patients with liver cirrhosis have reduced ability to hydroxylate triamterene, as evidenced by high plasma concentrations of triamterene and low concentrations of 4'-hydroxytriamterene sulfate. After administration of 200 mg of triamterene, peak plasma concentrations in eight patients without liver disease were 559 +/- 48 ng/mL and 2956 +/- 320 ng/mL for triamterene and 4'-hydroxytriamterene sulfate, respectively. In the seven patients with alcoholic cirrhosis, peak plasma concentrations of triamterene were increased to 1434 +/- 184 ng/mL, while the concentrations of the sulfate were reduced to 469 +/- 84 ng/mL. Renal clearance was also reduced in patients with cirrhosis: the clearance of triamterene and the sulfate were 2.8 +/- 0.7 and 38.0 +/- 6.6 mL/minute, respectively, compared with 14.4 +/- 1.5 and 116.7 +/- 11.6 mL/ minute, respectively, in patients without liver disease.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V108 278 (2016)


For more Absorption, Distribution and Excretion (Complete) data for Triamterene (12 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Triamterene undergoes phase I metabolism involving hydroxylation, via CYP1A2 activity, to form 4'-hydroxytriamterene. 4'-Hydroxytriamterene is further transformed in phase II metabolism mediated by cytosolic sulfotransferases to form the major metabolite, 4-hydroxytriamterene sulfate, which retains a diuretic activity. Both the plasma and urine levels of this metabolite greatly exceed triamterene levels while the renal clearance of the sulfate conjugate was les than that of triamterene; this low renal clearance of the sulfate conjugate as compared with triamterene may be explained by the low unbound fraction of the metabolite in plasma.


The metabolic and excretory fate of triamterene has not been fully determined. The drug is reportedly metabolized to 6-p-hydroxytriamterene and its sulfate conjugate.

American Society of Health-System Pharmacists; Drug Information 2018. Bethesda, MD. 2018, p. 2878


The kinetics of triamterene and its active phase II metabolite were studied in 32 patients with various degrees of impaired renal function; the creatinine clearances ranged from 135 to 10 mL/min. The area under the plasma concentration-time curves (AUC) for triamterene were not influenced by kidney function, but the AUCs for the effective metabolite OH-TA-ester were significantly elevated in renal failure, indicating accumulation of the metabolite. Urinary recovery of triamterene and its metabolite over a 48 hr collection period was significantly reduced in renal failure. This is considered to be due to delayed urinary excretion, corresponding to reduced renal clearance. The renal clearance of the native drug exceeded that of the metabolite, because of their different protein binding, 55% for triamterene and 91% for the metabolite. The latter is eliminated almost exclusively via tubular secretion and extra-renal elimination is less important. ...

PMID:6861860 Knauf H et al; Eur J Clin Pharmacol 24 (4): 453-6 (1983)


Patients with liver cirrhosis have reduced ability to hydroxylate triamterene, as evidenced by high plasma concentrations of triamterene and low concentrations of 4'-hydroxytriamterene sulfate. After administration of 200 mg of triamterene, peak plasma concentrations in eight patients without liver disease were 559 +/- 48 ng/mL and 2956 +/- 320 ng/mL for triamterene and 4'-hydroxytriamterene sulfate, respectively. In the seven patients with alcoholic cirrhosis, peak plasma concentrations of triamterene were increased to 1434 +/- 184 ng/mL, while the concentrations of the sulfate were reduced to 469 +/- 84 ng/mL. Renal clearance was also reduced in patients with cirrhosis: the clearance of triamterene and the sulfate were 2.8 +/- 0.7 and 38.0 +/- 6.6 mL/minute, respectively, compared with 14.4 +/- 1.5 and 116.7 +/- 11.6 mL/ minute, respectively, in patients without liver disease.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V108 278 (2016)


5.7 Biological Half-Life

The half-life of the drug in plasma ranges from 1.5 to 2 hours. In a pharmacokinetic study involving healthy volunteers, the terminal half-lives for triamterene and 4-hydroxytriamterene sulfate were 255 42 and 188 70 minutes, respectively, after intravenous infusion of the parent drug.


The plasma half-life of triamterene is 100-150 minutes.

American Society of Health-System Pharmacists; Drug Information 2018. Bethesda, MD. 2018, p. 2878


5.8 Mechanism of Action

Triamterene inhibits the epithelial sodium channels (ENaC) located on the lumenal side in the late distal convoluted tubule and collecting tubule, which are transmembrane channels that normally promotes sodium uptake and potassium secretion. In the late distal tubule to the collecting duct, sodium ions are actively reabsorbed via ENaC on the lumnial membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase, with water following passively. Triamterene exerts a diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium ions in exchange for potassium and hydrogen ions and its natriuretic activity is limited by the amount of sodium reaching its site of action. Its action is antagonistic to that of adrenal mineralocorticoids, such as aldosterone, but it is not an inhibitor or antagonist of aldosterone. Triamterene maintains or increases the sodium excretionm, thereby increasing the excretion of water, and reduces the excess loss of potassium, hydrogen and chloride ions by inhibiting the distal tubular exchange mechanism. Due to its diuretic effect, triamterene rapidly and reversibly reduces the lumen-negative transepithelial potential difference by almost complete abolition of Na+ conductance without altering K+ conductance. This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion. Triamterene is similar in action to [amiloride] but, unlike amiloride, increases the urinary excretion of magnesium.


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