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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1983 Mar;15(3):303–309. doi: 10.1111/j.1365-2125.1983.tb01503.x

Reduced clearance of triazolam in old age: relation to antipyrine oxidizing capacity.

D J Greenblatt, M Divoll, D R Abernethy, L J Moschitto, R B Smith, R I Shader
PMCID: PMC1427766  PMID: 6133545

Abstract

Thirty-three healthy male and female volunteers aged 21 to 87 years received a single 0.5 mg oral dose of triazolam. Plasma triazolam concentrations were measured in multiple samples drawn during 24 h after the dose. Mean triazolam elimination half-life was not significantly different between young and elderly men (3.0 vs 4.6 h), nor between young and elderly women (2.7 vs 3.2 h). However, apparent oral clearance of triazolam was significantly reduced in elderly as compared to young groups of both sexes, leading to higher peak plasma concentrations and increased total area under the curve. Values of half-life and clearance of antipyrine, a low-extraction hepatically oxidized compound, were poorly correlated with those of triazolam (r = 0.34 and 0.44, respectively), suggesting different mechanisms controlling age-related changes in clearance of these two hepatically oxidized drugs.

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Selected References

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  1. Abernethy D. R., Greenblatt D. J., Zumbo A. M. Antipyrine determination in human plasma by gas--liquid chromatography using nitrogen--phosphorus detection. J Chromatogr. 1981 May 8;223(2):432–437. [PubMed] [Google Scholar]
  2. Allen M. D., Greenblatt D. J., Harmatz J. S., Shader R. I. Desmethyldiazepam kinetics in the elderly after oral prazepam. Clin Pharmacol Ther. 1980 Aug;28(2):196–202. doi: 10.1038/clpt.1980.150. [DOI] [PubMed] [Google Scholar]
  3. Bach B., Hansen J. M., Kampmann J. P., Rasmussen S. N., Skovsted L. Disposition of antipyrine and phenytoin correlated with age and liver volume in man. Clin Pharmacokinet. 1981 Sep-Oct;6(5):389–396. doi: 10.2165/00003088-198106050-00005. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Greenblatt D. J., Allen M. D., Harmatz J. S., Shader R. I. Diazepam disposition determinants. Clin Pharmacol Ther. 1980 Mar;27(3):301–312. doi: 10.1038/clpt.1980.40. [DOI] [PubMed] [Google Scholar]
  6. Greenblatt D. J., Allen M. D., Locniskar A., Harmatz J. S., Shader R. I. Lorazepam kinetics in the elderly. Clin Pharmacol Ther. 1979 Jul;26(1):103–113. doi: 10.1002/cpt1979261103. [DOI] [PubMed] [Google Scholar]
  7. Greenblatt D. J., Divoll M., Abernethy D. R., Harmatz J. S., Shader R. I. Antipyrine kinetics in the elderly: prediction of age-related changes in benzodiazepine oxidizing capacity. J Pharmacol Exp Ther. 1982 Jan;220(1):120–126. [PubMed] [Google Scholar]
  8. Greenblatt D. J., Divoll M., Harmatz J. S., MacLaughlin D. S., Shader R. I. Kinetics and clinical effects of flurazepam in young and elderly noninsomniacs. Clin Pharmacol Ther. 1981 Oct;30(4):475–486. doi: 10.1038/clpt.1981.191. [DOI] [PubMed] [Google Scholar]
  9. Greenblatt D. J., Divoll M., Harmatz J. S., Shader R. I. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther. 1980 Oct;215(1):86–91. [PubMed] [Google Scholar]
  10. Greenblatt D. J., Divoll M., Harmatz J. S., Shader R. I. Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular, and oral lorazepam. J Pharm Sci. 1982 Feb;71(2):248–252. doi: 10.1002/jps.2600710227. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Greenblatt D. J., Divoll M., Puri S. K., Ho I., Zinny M. A., Shader R. I. Clobazam kinetics in the elderly. Br J Clin Pharmacol. 1981 Nov;12(5):631–636. doi: 10.1111/j.1365-2125.1981.tb01281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Greenblatt D. J., Locniskar A. Spectrophotometric assay of antipyrine in plasma: a reevaluation. Int J Clin Pharmacol Biopharm. 1979 Sep;17(9):401–404. [PubMed] [Google Scholar]
  14. 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]
  15. Greenblatt D. J., Shader R. I., Franke K., MacLaughlin D. S., Harmatz J. S., Allen M. D., Werner A., Woo E. Pharmacokinetics and bioavailability of intravenous, intramuscular, and oral lorazepam in humans. J Pharm Sci. 1979 Jan;68(1):57–63. doi: 10.1002/jps.2600680119. [DOI] [PubMed] [Google Scholar]
  16. Greenblatt D. J., Shader R. I., MacLeod S. M., Sellers E. M., Franke K., Giles H. G. Absorption of oral and intramuscular chlordiazepoxide. Eur J Clin Pharmacol. 1978 Jun 19;13(4):267–274. doi: 10.1007/BF00716362. [DOI] [PubMed] [Google Scholar]
  17. Liddell D. E., Williams F. M., Briant R. H. Phenazone (antipyrine) metabolism and distribution in young and elderly adults. Clin Exp Pharmacol Physiol. 1975 Nov-Dec;2(6):481–487. doi: 10.1111/j.1440-1681.1975.tb01853.x. [DOI] [PubMed] [Google Scholar]
  18. O'Malley K., Crooks J., Duke E., Stevenson I. H. Effect of age and sex on human drug metabolism. Br Med J. 1971 Sep 11;3(5775):607–609. doi: 10.1136/bmj.3.5775.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ochs H. R., Greenblatt D. J., Divoll M., Abernethy D. R., Feyerabend H., Dengler H. J. Diazepam kinetics in relation to age and sex. Pharmacology. 1981;23(1):24–30. doi: 10.1159/000137524. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Shader R. I., Greenblatt D. J., Ciraulo D. A., Divoll M., Harmatz J. S., Georgotas A. Effect of age and sex on disposition of desmethyldiazepam formed from its precursor clorazepate. Psychopharmacology (Berl) 1981;75(2):193–197. doi: 10.1007/BF00432186. [DOI] [PubMed] [Google Scholar]
  22. Stevenson I. H. Factors influencing antipyrine elimination. Br J Clin Pharmacol. 1977 Jun;4(3):261–265. doi: 10.1111/j.1365-2125.1977.tb00710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Vesell E. S. The antipyrine test in clinical pharmacology: conceptions and misconceptions. Clin Pharmacol Ther. 1979 Sep;26(3):275–286. doi: 10.1002/cpt1979263275. [DOI] [PubMed] [Google Scholar]
  24. Vestal R. E., Norris A. H., Tobin J. D., Cohen B. H., Shock N. W., Andres R. Antipyrine metabolism in man: influence of age, alcohol, caffeine, and smoking. Clin Pharmacol Ther. 1975 Oct;18(4):425–432. doi: 10.1002/cpt1975184425. [DOI] [PubMed] [Google Scholar]
  25. Vestal R. F. Pharmacology and aging. J Am Geriatr Soc. 1982 Mar;30(3):191–200. doi: 10.1111/j.1532-5415.1982.tb01303.x. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Wood A. J., Vestal R. E., Wilkinson G. R., Branch R. A., Shand D. G. Effect of aging and cigarette smoking on antipyrine and indocyanine green elimination. Clin Pharmacol Ther. 1979 Jul;26(1):16–20. doi: 10.1002/cpt197926116. [DOI] [PubMed] [Google Scholar]

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