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 (t_1/2) of 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 t_1/2, 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 monitor-ing of carbamazepine plasma levels provided.