Single- and multiple-dose pharmacokinetics of oral alprazolam in healthy smoking and nonsmoking men

Abstract

The effect of tobacco smoking on alprazolam pharmacokinetics is investigated. Ten healthy men (five smokers and five nonsmokers) between 19 and 42 years old received a single oral 1-mg alprazolam dose followed 48 hours later by alprazolam 0.5 mg every eight hours for six days. Multiple serum samples were collected following the initial dose and after the last 0.5-mg dose and analyzed by gas-liquid chromatography for alprazolam. Pharmacokinetic values were calculated, and mean data from the smoking and nonsmoking groups were compared. Mean plasma alprazolam concentrations during the single-dose phase were comparable between groups. During the multiple-dose phase, mean plasma concentrations were 15-30% lower in the smokers. Total body clearance of alprazolam was 24% greater and the apparent volume of distribution was 17% less in smokers. The elimination half-life was 49% greater in nonsmokers. These differences were not significant. Changes were not observed in elimination half-life or clearance after alprazolam cessation. Steady-state pharmacokinetic values during the multiple-dose phase correlated with values observed following the single dose. Although not significantly different, alprazolam elimination was more rapid in smokers than in nonsmokers.