Effect of a cocktail on diazepam absorption

Six healthy male or female volunteers ingested a single 5-mg tablet of diazepam with a typical ethanol-containing cocktail (1.5 ounces of 80-proof vodka plus 4 ounces of orange juice plus ice) or with a similar ethanol-free mixture (4 ounces of orange juice plus ice) in the fasting state on two occasions separated by at least 1 week. Diazepam concentrations in multiple plasma samples drawn from 15 min to 24 h after each dose were determined by electron-capture gas-liquid chromatography. Mean values of pharmacokinetic variables for diazepam taken without and with ethanol, respectively, were: peak plasma diazepam concentration, 221 vs. 208 ng/ml; time of peak concentration, 0.79 vs. 1.79 h after dosing (P<0.1); apparent lag time prior to start of absorption, 16.5 vs. 26.2 min; apparent first-order absorption half-life, 19.3 vs. 34.6 min. The completeness of diazepam absorption, judged by the area under the 24-h plasma concentration curve, was nearly identical for the two conditions. Thus, coadministration of diazepam with the ethanol cocktail tended to slow the rate of diazepam absorption, but did not influence the completeness of absorption. Pharmacodynamic synergism of ethanol and diazepam, if it exists, cannot be attributed to enhancement of the rate or completeness of diazepam absorption.