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. 1985 Jan;19(1):51–57. doi: 10.1111/j.1365-2125.1985.tb02612.x

Interaction of propoxyphene with diazepam, alprazolam and lorazepam.

D R Abernethy, D J Greenblatt, D S Morse, R I Shader
PMCID: PMC1463783  PMID: 2858217

Abstract

Healthy volunteers received single doses of three benzodiazepines (diazepam, 10 mg i.v.; alprazolam, 1.0 mg orally; lorazepam, 2 mg i.v.) on two occasions in random sequence. One trial was a control; for the other, subjects ingested propoxyphene, 65 mg every 6 h, for the duration of the benzodiazepine study. The kinetics of each benzodiazepine were determined from multiple plasma concentrations measured following each dose. For diazepam, propoxyphene produced a small and statistically insignificant prolongation of elimination half-life (43 vs 38 h) and reduction of total clearance (0.41 vs 0.47 ml min-1 kg-1). Propoxyphene significantly prolonged alprazolam half-life (18 vs 12 h, P less than 0.005) and reduced total clearance (0.8 vs 1.3 ml min-1 kg-1, P less than 0.005). Propoxyphene had no apparent influence on lorazepam half-life (13.4 vs 13.5 h) or clearance (1.5 vs 1.4 ml min-1 kg-1). Thus propoxyphene significantly impairs the clearance of alprazolam, biotransformed mainly by the oxidative reaction of aliphatic hydroxylation. Propoxyphene has far less effect on the oxidation of diazepam by N-demethylation, and has no apparent influence on lorazepam 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., Ochs H. R., Weyers D., Divoll M., Harmatz J. S., Shader R. I. Lorazepam and oxazepam kinetics in women on low-dose oral contraceptives. Clin Pharmacol Ther. 1983 May;33(5):628–632. doi: 10.1038/clpt.1983.85. [DOI] [PubMed] [Google Scholar]
  3. Abernethy D. R., Greenblatt D. J., Steel K., Shader R. I. Impairment of hepatic drug oxidation by propoxyphene. Ann Intern Med. 1982 Aug;97(2):223–224. doi: 10.7326/0003-4819-97-2-223. [DOI] [PubMed] [Google Scholar]
  4. Dam M., Kristensen C. B., Hansen B. S., Christiansen J. Interaction between carbamazepine and propoxyphene in man. Acta Neurol Scand. 1977 Dec;56(6):603–607. doi: 10.1111/j.1600-0404.1977.tb01465.x. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Greenblatt D. J., Divoll M., Abernethy D. R., Moschitto L. J., Smith R. B., Shader R. I. Alprazolam kinetics in the elderly. Relation to antipyrine disposition. Arch Gen Psychiatry. 1983 Mar;40(3):287–290. doi: 10.1001/archpsyc.1983.01790030057007. [DOI] [PubMed] [Google Scholar]
  8. Greenblatt D. J., Divoll M., Abernethy D. R., Ochs H. R., Shader R. I. Benzodiazepine kinetics: implications for therapeutics and pharmacogeriatrics. Drug Metab Rev. 1983;14(2):251–292. doi: 10.3109/03602538308991391. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Greenblatt D. J., Divoll M., Shader R. I. Automated gas chromatographic determination of plasma alprazolam concentrations. J Clin Psychopharmacol. 1983 Dec;3(6):366–368. [PubMed] [Google Scholar]
  11. 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]
  12. Greenblatt D. J., Ochs H. R., Lloyd B. L. Entry of diazepam and its major matabolite into cerebrospinal fluid. Psychopharmacology (Berl) 1980;70(1):89–93. doi: 10.1007/BF00432376. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Hansen B. S., Dam M., Brandt J., Hvidberg E. F., Angelo H., Christensen J. M., Lous P. Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man. Acta Neurol Scand. 1980 Jun;61(6):357–367. doi: 10.1111/j.1600-0404.1980.tb01505.x. [DOI] [PubMed] [Google Scholar]
  15. Kutt H. Biochemical and genetic factors regulating dilantin metabolism in man. Ann N Y Acad Sci. 1971 Jul 6;179:705–722. doi: 10.1111/j.1749-6632.1971.tb46946.x. [DOI] [PubMed] [Google Scholar]
  16. Peterson G. R., Hostetler R. M., Lehman T., Covault H. P. Acute inhibition of oxidative drug metabolism by propoxyphene (Darvon). Biochem Pharmacol. 1979 Jun 1;28(11):1783–1789. doi: 10.1016/0006-2952(79)90541-0. [DOI] [PubMed] [Google Scholar]

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