1. Identify main metabolic enzymes involved in elimination of clozapine. a) Tabulate median clozapine maximal plasma concentrations (Cmax), area under plasma concentration-time curve (AUC) and clearance (Dose/AUC) in non-smokers vs. heavy

smokers (>20 cigarettes/day). Assess percent change in these parameters in smoker vs. non-smoker patients. Explain reasons for potential differences in parameters between smokers and non-smokers. b) Comment whether you would recommend a change in clozapine dose in heavy smokers and why.