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. 1983 Dec;16(6):743–746. doi: 10.1111/j.1365-2125.1983.tb02256.x

Differential effect of isoniazid on triazolam oxidation and oxazepam conjugation.

H R Ochs, D J Greenblatt, M Knüchel
PMCID: PMC1428351  PMID: 6140941

Abstract

Healthy volunteers received a single dose of triazolam (0.5 mg) or oxazepam (30 mg) on two occasions, once in the control state and again during coadministration of isoniazid (INH) base, 180 mg day. INH coadministration prolonged triazolam half-life (3.3 vs 2.5 h, P less than 0.05) and increased total area under the curve (38.6 vs 26.5 ng ml-1 h, P less than 0.01) consistent with a reduction of apparent oral clearance (3.9 vs 6.8 ml min-1 kg-1, 0.05 less than P less than 0.1). INH coadministration had no influence on the kinetics of oxazepam. INH impairs hepatic microsomal oxidation of triazolam, leading to reduced first-pass hepatic extraction as well as prolonged half-life. However INH had no influence on oxazepam conjugation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abernethy D. R., Greenblatt D. J., Divoll M., Ameer B., Shader R. I. Differential effect of cimetidine on drug oxidation (antipyrine and diazepam) vs. conjugation (acetaminophen and lorazepam): prevention of acetaminophen toxicity by cimetidine. J Pharmacol Exp Ther. 1983 Mar;224(3):508–513. [PubMed] [Google Scholar]
  2. Abernethy D. R., Greenblatt D. J., Divoll M., Moschitto L. J., Harmatz J. S., Shader R. I. Interaction of cimetidine with the triazolobenzodiazepines alprazolam and triazolam. Psychopharmacology (Berl) 1983;80(3):275–278. doi: 10.1007/BF00436169. [DOI] [PubMed] [Google Scholar]
  3. Eberts F. S., Jr, Philopoulos Y., Reineke L. M., Vliek R. W. Triazolam disposition. Clin Pharmacol Ther. 1981 Jan;29(1):81–93. doi: 10.1038/clpt.1981.14. [DOI] [PubMed] [Google Scholar]
  4. Greenblatt D. J. Clinical pharmacokinetics of oxazepam and lorazepam. Clin Pharmacokinet. 1981 Mar-Apr;6(2):89–105. doi: 10.2165/00003088-198106020-00001. [DOI] [PubMed] [Google Scholar]
  5. Greenblatt D. J., Divoll M., Abernethy D. R., Moschitto L. J., Smith R. B., Shader R. I. Reduced clearance of triazolam in old age: relation to antipyrine oxidizing capacity. Br J Clin Pharmacol. 1983 Mar;15(3):303–309. doi: 10.1111/j.1365-2125.1983.tb01503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Greenblatt D. J., Divoll M., Moschitto L. J., Shader R. I. Electron-capture gas chromatographic analysis of the triazolobenzodiazepines alprazolam and triazolam. J Chromatogr. 1981 Sep 11;225(1):202–207. doi: 10.1016/s0378-4347(00)80261-3. [DOI] [PubMed] [Google Scholar]
  7. Greenblatt D. J., Franke K., Shader R. I. Analysis of lorazepam and its glucuronide metabolite by electron-capture gas--liquid chromatography. Use in pharmacokinetic studies of lorazepam. J Chromatogr. 1978 Sep 1;146(2):311–320. [PubMed] [Google Scholar]
  8. Greenblatt D. J., Sellers E. M., Shader R. I. Drug therapy: drug disposition in old age. N Engl J Med. 1982 May 6;306(18):1081–1088. doi: 10.1056/NEJM198205063061804. [DOI] [PubMed] [Google Scholar]
  9. Kutt H., Brennan R., Dehejia H., Verebely K. Diphenylhydantoin intoxication. A complication of isoniazid therapy. Am Rev Respir Dis. 1970 Mar;101(3):377–384. doi: 10.1164/arrd.1970.101.3.377. [DOI] [PubMed] [Google Scholar]
  10. Miller R. R., Porter J., Greenblatt D. J. Clinical importance of the interaction of phenytoin and isoniazid: a report from the Boston Collaborative Drug Surveillance Program. Chest. 1979 Mar;75(3):356–358. doi: 10.1378/chest.75.3.356. [DOI] [PubMed] [Google Scholar]
  11. Muakkassah S. F., Bidlack W. R., Yang W. C. Mechanism of the inhibitory action of isoniazid on microsomal drug metabolism. Biochem Pharmacol. 1981 Jun 15;30(12):1651–1658. doi: 10.1016/0006-2952(81)90393-2. [DOI] [PubMed] [Google Scholar]
  12. Ochs H. R., Greenblatt D. J., Roberts G. M., Dengler H. J. Diazepam interaction with antituberculosis drugs. Clin Pharmacol Ther. 1981 May;29(5):671–678. doi: 10.1038/clpt.1981.94. [DOI] [PubMed] [Google Scholar]
  13. Pakes G. E., Brogden R. N., Heel R. C., Speight T. M., Avery G. S. Triazolam: a review of its pharmacological properties and therapeutic efficacy in patients with insomnia. Drugs. 1981 Aug;22(2):81–110. doi: 10.2165/00003495-198122020-00001. [DOI] [PubMed] [Google Scholar]
  14. Valsalan V. C., Cooper G. L. Carbamazepine intoxication caused by interaction with isoniazid. Br Med J (Clin Res Ed) 1982 Jul 24;285(6337):261–262. doi: 10.1136/bmj.285.6337.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Weber W. W., Hein D. W. Clinical pharmacokinetics of isoniazid. Clin Pharmacokinet. 1979 Nov-Dec;4(6):401–422. doi: 10.2165/00003088-197904060-00001. [DOI] [PubMed] [Google Scholar]
  16. Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]

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