Alprazolam pharmacokinetics in alcoholic liver disease

Alprazolam, a triazolobenzodiazepine, was administered to 17 patients with alcoholic liver disease. The pharmacokinetic parameters derived from plasma alprazolam concentrations were compared with data obtained from 17 normal subjects who were matched for age and sex. The rate of absorption of alprazolam was slower in patients with alcoholic liver disease. The time of maximum serum concentration was 3.3 hours, compared with 1.5 hour in normals (P less than 0.02). The maximum concentrations, however, did not differ (18.4 vs. 17.2 micrograms/ml). The elimination half-life of drug was longer in the patients (19.7 hours) than in the normal subjects (11.4 hours), while the clearance of the drug was slower in the patients with alcoholic liver disease (0.6 vs 1.2 ml/min/kg). The volumes of distribution (area) did not differ between the two groups (1.1 vs. 1.2 liter/kg). The changes in elimination half-life and clearance indicate that the metabolism of the drug is slowed in patients with alcoholic liver disease.