Therapeutic drug monitoring of amitriptyline: impact of age, smoking and contraceptives on drug and metabolite levels in bulimic women.

Concentrations of amitriptyline (AT), nortriptyline (NT) and E-10-hydroxynortriptyline (E-10-OH-NT) were measured in 18 women with bulimia receiving 100 mg AT/day for at least 6 wk. After onset of treatment between days 36 and 57 there is a decrease in AT and an increase in E-10-OH-NT concentrations, probably due to an autoinductive effect on hydroxylation. The estimated mean (+/- SD; range; n) elimination half-life time of AT was 14.0 (+/- 7.8 h; 7.5-38.5 h; 14). On day 36, AT concentrations in females using oral contraceptives (OC) were higher than in non-users of OC, which indicates inhibition of AT metabolism by OC. In all smokers the E-10-OH-NT concentrations on day 36 were lower than in non-smokers. Our findings suggest induction of N-demethylation and glucuronidation by smoke components.