Carbamazepine Phakmacokinetics in Obese and Lean Subjects

Abstract

Objective: To compare carbamazepine pharmacokinetic parameters between obese and lean subjects following the administration of a single 200-mg tablet. Design: Single-dose intervention, open study. Setting: Teaching university hospital. Subjects: Eighteen obese (group A) otherwise healthy subjects, referred to the metabolic outpatient clinic, and 13 healthy lean (group B) volunteers. Inclusion criterion for the obese subjects was a body mass index (BMI = weight/height2) of more than 30 kg/m2. In the obese group, mean ± SD total body weight (TBW), BMI, and percent of ideal body weight (IBW) were 111.4 ± 19.9 kg, 38.8 ± 6.0 kg/m2, and 182.7% ± 30.7%, respectively. These values were significantly greater than the respective values of 63.2 ± 8.3 kg, 22.4 ± 1.6 kg/m2, and 105.8% ± 5.8% obtained in the lean group (p < 0.001). Intervention: Single-dose oral administration of carbamazepine 200-mg tablet (Teril, Taro, Israel). Outcomes: Carbamazepine elimination half-life (t1/2), apparent volume of distribution (Varea/F), and its oral clearance (Clpo/F) were derived from the drug concentration-time curves. Results: Carbamazepine Varea/F and t1/2 were significantly greater in group A than in group B (98.4 ± 26.9 vs. 60.7 ± 8.5 L, respectively, p < 0.001; and 59.4 ± 14.7 vs. 31.0 ± 5.0 h, respectively, p < 0.001), but its Clpo/F was reduced only slightly in obese as compared with lean subjects (19.8 ± 5.2 vs. 23.0 ± 4.6 mL/min, respectively, p = 0.07). Correction for IBW yielded similar results for Varea/F and t1/2, but Clpo/F per kg of IBW was significantly smaller in the obese than in the lean subjects (0.32 ± 0.07 vs. 0.39 ± 0.06 mL/min/kg of IBW, respectively, p < 0.02). Linear correlations were observed between Varea/F and TBW for both group A (r = 0.92, p < 0.001) and group B (r = 0.77, p < 0.002). Conclusions: In comparison with lean subjects, carbamazepine Varea/F is significantly greater in obese subjects and its t1/2 is markedly prolonged. The minor nonsignificant effect of obesity on carbamazepine Clpo/F suggests that in obese subjects the carbamazepine daily dose should be based on IBW, not on TBW.