Interaction of propoxyphene with diazepam, alprazolam and lorazepam.

DR Abernethy, DJ Greenblatt, DS Morse, RI Shader

Research output: Contribution to journalArticlepeer-review

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. 1985 The British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalBritish Journal of Clinical Pharmacology
Volume19
Issue number1
DOIs
StatePublished - Jan 1985

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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