Interaction of propoxyphene with diazepam, alprazolam and lorazepam

Br J Clin Pharmacol. 1985 Jan;19(1):51-7. doi: 10.1111/j.1365-2125.1985.tb02612.x.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alprazolam
  • Anti-Anxiety Agents / metabolism*
  • Benzodiazepines / metabolism
  • Dextropropoxyphene / pharmacology*
  • Diazepam / metabolism
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Kinetics
  • Lorazepam / metabolism
  • Male
  • Metabolic Clearance Rate / drug effects
  • Middle Aged


  • Anti-Anxiety Agents
  • Benzodiazepines
  • Lorazepam
  • Diazepam
  • Dextropropoxyphene
  • Alprazolam