Theophylline and antipyrine disposition in smoking and non‐smoking epileptic subjects.

Abstract

Theophylline and antipyrine disposition has been compared in smoking epileptic patients, non-smoking epileptic patients and non-smoking healthy volunteers. Although clear differences in drug clearance and half-life were evident as a result of anticonvulsant drug therapy, no effect of smoking was discernible. Thus, additive effects from induction of the hepatic microsomal monooxygenase system in man by anticonvulsant drugs and polycyclic aromatic hydrocarbons (in cigarette smoke) were not evident.

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].…”