Plasma kinetics of carbamazepine and its epoxide metabolite in man after single and multiple doses

Carbamazepine (Tegretol) was administered orally to four patients as a single dose, and one week later three times daily for 15-21 days. The plasma half-lives of the drug were shorter in all patients after multiple doses (20.9 +/- 5.0 hours) than after the initial single dose (35.6 +/- 15.3 hours). During the multiple dose the plasma concentrations of the metabolite carbamazepine-10,11-epoxide followed those of the parent drug. The steady-state plasma concentrations expected during multiple doses were calculated from the pharmacokinetic parameters obtained in the single dose studies. The calculated levels were higher (17.2+/-7.2 mug/ml) than the observed maximal concentrations (8.4+/-1.6 mug/ml on day 4), which were obtained 3-4 days after starting the multiple doses. The levels tended to decrease further during the experimental period. The results suggest that carbamazepine induces its own metabolism in man.