Lack of influence of cigarette smoking on triazolam pharmacokinetics.

Abstract

The influence of cigarette smoking on the pharmacokinetics of a single dose of the triazolobenzodiazepine hypnotic triazolam was evaluated in 12 healthy nonsmoking male volunteers and in 12 male subjects, matched for age, height and weight, who smoked an average of 24 cigarettes a day (range: 15‐30). Triazolam kinetics were determined from multiple serum concentrations measured during 15 h after a single 0.5 mg dose. There were no significant differences between nonsmoking controls and cigarette smokers in the peak serum triazolam concentration (4.64 vs 4.73 ng ml‐1), the time of peak concentration (0.98 vs 1.0 h after dosage), elimination half‐life (2.8 vs 2.5 h), or oral clearance of triazolam (506 vs 627 ml min‐1). Likewise there were no significant differences between groups in the extent of triazolam binding to serum protein (18.8 vs 18.5% unbound). Altered pharmacodynamics of triazolam in cigarette smokers are not likely to be explained by altered pharmacokinetics.

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

“…The hydrocarbons contained in tobacco smoke induce hepatic microsomal drug-me tabolizing enzymes, causing an enhanced clearance of a number of drugs in cigarette smokers as compared to nonsmoking control subjects [Murphy et al, 1988;Vestal et al, 1975;Loft et al, 1988;Gardner et al, 1983;Cusack et al, 1985], However, the inducing effects of smoking are not observed for all drugs [Acheson et al, 1987;Ochs et al, 1985Ochs et al, , 1986Ochs et al, , 1987Schaaf et al, 1987], We evaluated the influence of cigarette smoking on the kinetics of single intravenous doses of antipyrine and acetaminophen. Since the studies were performed in the same labora tory using similar (and in some cases identi cal) groups of subjects, differential effects of smoking on the kinetics of the two drugs are unlikely to be attributable to interlaboratory méthodologie differences, or to different characteristics of the study populations.…”

“…1982;D'Arcy, 1984;Miller, 1989]. Some studies also suggest a reduced drug effect or the need to increase drug dosage in cigarette smoking populations as compared to nonsmokers [Jick, 1974;Miller, 1977], How ever, the altered drug disposition by ciga rette smoking is not uniformly reported, and some studies show a small or negligible in fluence of smoking [Acheson et al, 1987;Ochs et al, 1985Ochs et al, , 1986Ochs et al, , 1987, Antipyrine and acetaminophen have been used as marker compounds to evaluate drugmetabolizing activity. Antipyrine is bio transformed by a series of parallel oxidative mechanisms, leading to three principal me tabolites formed by déméthylation and/or hydroxylation [Danhof et al, 1982;Eichelbaum et al, 1983;Boobis et al, 1981].…”

Clinically significant pharmacokinetic drug interactions with benzodiazepines

“…Cigarette smoking can result in as much as a three‐fold increase in CYP1A2 activity, principally due to nicotine and the polycyclic aromatic hydrocarbons formed during combustion (82). However, it is currently reported that cigarette smoking does not affect the metabolism of BZPs (83–85).…”