Rapid reversibility of autoinduction of carbamazepine metabolism after temporary discontinuation.

Abstract

Patients in whom carbamazepine (CBZ) monotherapy is discontinued for preoperative EEG/video monitoring often display toxicity if their previous maintenance dosage is resumed, even after a few days without CBZ. To determine whether this is due to rapid reversibility of autoinduction of CBZ metabolism, single-dose studies of CBZ pharmacokinetics were performed before and after discontinuation for monitoring in 6 adults receiving CBZ monotherapy. The CBZ-free period was 5.7 +/- 1.1 days (mean +/- SD). The pharmacokinetic parameters of CBZ before and after discontinuation were volume of distribution (Vd) 1.28 +/- 0.29 versus 1.22 +/- 0.331/kg (NS), elimination half-life (t1/2) 13.7 +/- 1.67 versus 22.2 +/- 2.36 h (p < 0.001), and clearance (Cl) 1.54 +/- 0.39 versus 0.92 +/- 0.32 L/kg/day (p = 0.012). Assuming that deinduction is a first-order process, a deinduction t1/2 of 3.84 days was obtained by log linear regression analysis. We showed that after CBZ discontinuation half of the enzymatic autoinduction is already lost after 3.84 days, indicating very rapid deinduction. Our results also provide the necessary information to predict clearance and appropriate dosage reduction for CBZ at time of reintroduction.