Interaction of propoxyphene with diazepam, alprazolam and lorazepam.
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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D000328:Adult; D000525:Alprazolam; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001569:Benzodiazepines / Q000378:metabolism; D011431:Dextropropoxyphene / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008140:Lorazepam / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D008140:Lorazepam; D003975:Diazepam; D011431:Dextropropoxyphene; D000525:Alprazolam