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.