Single- and multiple-dose pharmacokinetics of oral alprazolam in healthy smoking and nonsmoking men
Smith, R.B.; Gwilt, P.R.; Wright, C.E.
Clinical Pharmacy 2(2): 139-143
1983
ISSN/ISBN: 0278-2677 PMID: 6883942 Document Number: 198617
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.