Cytochromes P450: Roles in the Biotransformation of Chemicals in Cigarette Smoke and Impact of Smoking Cessation on Concurrent Drug Therapy

Abstract

AbstractCigarette smoke contains polycyclic aromatic hydrocarbons (PAHs) that activate the expression of cytochrome P450 family 1 (CYP1) enzymes in liver and other tissues; this process is dependent on the aryl hydrocarbon receptor (AhR) transcription factor. An important CYP1 enzyme, CYP1A2, has a critical role in the oxidation of drugs such as clozapine, olanzapine and theophylline; these drugs exhibit a high incidence of adverse effects that are linked to plasma concentrations. This article reviews the impact of smoking and smoking cessation on therapy with toxic drugs that undergo CYP-mediated elimination. PAHs in cigarette smoke activate the AhR and upregulate CYP1A2, which enhances the clearance of these drugs, diminishes their efficacy and necessitates the use of higher doses. However, smoking cessation decreases PAH exposure, which leads to a decline in clearance of CYP1A2 substrate drugs. Dose reductions and close therapeutic monitoring for such drugs are recommended in patients who cease smoking.