CARBAMAZEPINE PHARMACOKINETICS IN OBESE AND LEAN SUBJECTS

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/height(2)) of more than 30 kg/m(2). 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/m(2), 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/m(2), 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 (t(1/2)), apparent volume of distribution (V-area/F), and its oral clearance (Cl-po/F) were derived from the drug concentration-time curves. RESULTS: Carbamazepine V-area/F and t(1/2) 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 Cl-po/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 V-area/F and t(1/2), but Cl-po/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 V-area/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 V-area/F is significantly greater in obese subjects and its t(1/2) is markedly prolonged. The minor nonsignificant effect of obesity on carbamazepine Cl-po/F suggests that in obese subjects the carbamazepine daily dose should be based on IBW, not on TBW.