Objective The study was to investigate the relationship between
clozapine disposition and CYP1A2 activities by caffeine
test Methods Nine male normal volunteers (5 smokers) took a single oral dose of 150 mg caffeine and plasma samples were collected at the end of 5th hour after administration of caffeine With a washout interval of two days, the subjects received a 10 mg single oral dose of
clozapine Results The mean clozapine AUC 0,24 , t 1/2 , and T max , were (268±78) mg·h -1 ·L -1 , (28±10) h, and (2 1±0 8) h, respectively The indexes of CYP1A2 activities, by the ratios of paraxanthine (17X) and caffeine (137X) in plasma, were
correlated with reciprocals of clozapine AUC 0,24 ( n =9, r =0 667, P <0 05) The clozapine AUC 0,24 of smokers were significantly lower than no smokers ( t =2 42, P <0 05) Conclusions It is suggested that CYP1A2 may be involved in clozapine disposition in vivo Smoking could induce the enzymes of clozapine metabolism Monitoring of clozapine plasma concentration is recommended in the patients treated at same time with other drugs affecting CYP1A2