Influence of Cigarette Smoking Habit on Clozapine-to-Norclozapine Ratio in Male Patients

Abstract

Objective: This study aimed to evaluate the influence of cigarette smoking habit on the clozapine (CLZ)-to-norclozapine (norCLZ) ratio in male patients. Methods: The sample consisted of plasma concentration of CLZ and norCLZ data set. The mean values of CLZ, norCLZ, and CLZ-to-norCLZ, between male patients who smoke versus nonsmokers were compared. Findings: CLZ mean plasma level of 142 ± 80 ng/ml and 305 ± 159 ng/ml, norCLZ mean plasma level of 93 ± 72 ng/ml and 234 ± 62 ng/ml, and mean CLZ-to-norCLZ plasma level ratio of 2.1 ± 1.1 and 1.5 ± 0.5, were obtained respectively for male patients who smoke and nonsmokers. Conclusion: This study has shown a significant decrease in CLZ and norCLZ plasma levels, and an increase in the CLZ-to-norCLZ ratio, in smokers as compared to nonsmokers, due to an increase in the clearance of CLZ and norCLZ by smoking induction of CYP 1A2 and glucuronidation by uridyl glucuronyl transferase enzymes (UGT), mainly UGT 1A4, respectively, as the most probable cause.