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/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.