Enhancement of propoxyphene bioavailability by ethanol. Relation to psychomotor and cognitive function in healthy volunteers

Abstract

The interaction between a single oral dose of 130 mg propoxyphene and 0.5 g/kg body weight ethanol was investigated in 12 healthy male volunteers by 9 objective performance tests, 8 visual analogue self-rating scales and the measurement of plasma propoxyphene, norpropoxyphene and ethanol concentrations, using a double-blind threeway crossover design. Volunteers were each given one of three treatments, propoxyphene + ethanol, placebo + ethanol and propoxyphene alone, separated by a two week interval. The performance tests were completed before and 1.25 and 4 h after drug intake, and the self-rating scales before and 1.25, 4 and 10 h after it. Ethanol was shown to enhance the bioavailability of propoxyphene by 25% probably by reducing its first-pass metabolism. However, despite this pharmacokinetic effect no pharmacodynamic interaction was found. Subjective ratings disclosed that the effect of ethanol on physical and mental sedation predominated over the effects of propoxyphene.