Pharmacokinetic interaction of abacavir (1592U89) and ethanol in human immunodeficiency virus-infected adults

While in vitro results at clinically relevant concentrations do not predict abacavir (1592U89) interactions with drugs highly metabolized by cytochrom e P450, the potential does exist for a pharmacokinetic interaction between abacavir and ethanol, as both are metabolized by alcohol dehydrogenase. Twe nty-five subjects were enrolled in an open-label, randomized, three-way-cro ssover, phase I study of human immunodeficiency virus-infected male subject s. The three treatments were administration of (i) 600 mg of abacavir, (ii) 0.7 g of ethanol per kg of body weight, and (iii) 600 mg of abacavir and 0 .7 g of ethanol per kg, Twenty-four subjects completed the study with no un expected adverse events reported. Ethanol pharmacokinetic parameters were u nchanged with abacavir coadministration. The geometric least squares mean a rea under the concentration curve extrapolated to infinite time for abacavi r increased 41% (from 11.07 to 15.62 mu g.h/ml), and the half-life increase d 26% (from 1.42 to 1.79 h) in the presence of ethanol (mean ethanol maximu m concentration in plasma of 498 mu g/ml). The percentages of abacavir dose recovered in urine as abacavir and its two major metabolites were each alt ered in the presence of ethanol, but there was no change in the total perce ntage (approximate to 50%) of administered dose recovered in the 12-h colle ction interval. In conclusion, while a single 600-mg dose of abacavir does not alter blood ethanol concentration, ethanol does increase plasma abacavi r concentrations.