SIGNIFICANT WEIGHT-REDUCTION IN OBESE SUBJECTS ENHANCES CARBAMAZEPINE ELIMINATION

Single-dose (200 mg) carbamazepine pharmacokinetics was evaluated in six obese, otherwise healthy subjects, before and after a mean +/- SEM weight reduction of 30.0 +/- 5.0 kg over 11.3 +/- 1.2 months. After weight loss the mean +/- SEM plasma elimination half-life (t1/2) or carbamazepine was significantly shortened (60.3 +/- 3.1 versus 30.8 +/- 3.3 hours, p < 0.01) and the total plasma clearance (CL) increased (20.4 +/- 1.8 versus 31.6 +/- 5.0 ml/min, p < 0.05). The apparent volume of distribution (V(area)) decreased (106.2 +/- 9.9 versus 77.7 +/- 4.5 L, p < 0.01); however, no difference was evident when carbamazepine V(area) was corrected for body weight. In addition, weight loss coincided in all participants with a complete sonographic disappearance of the inital fatty liver infiltration noted on enrollment. In conclusion, obesity associated with fatty liver presents an enlarged carbamazepine V(area), prolonged carbamazepine t1/2, and reduced carbamazepine CL. Whenever carbamazepine is initiated in obese subjects, steady-state concentrations should be expected only after twice the time required to achieve steady state in lean subjects. Thus carbamazepine maintenance dose should be reduced, dose interval prolonged, and monitoring of carbamazepine plasma levels provided.