Steady-state Carbamazepine Pharmacokinetics following Oral and Stable-Labeled Intravenous Administration in Epilepsy Patients: Effect of Race and Sex

Carbamazepine is a widely prescribed antiepileptic drug. Due to a lack of an intravenous formulation, its absolute bioavailability, absolute clearance, and half-life in patients at steady state have not been determined. We developed an intravenous, stable-labeled (SL) formulation in order to characterize carbamazepine pharmacokinetics in patients. Ninety-two patients received a 100 mg infusion of SL-carbamazepine as part of their morning dose. Blood samples were collected up to 96 hours after drug administration. Plasma drug concentrations were measured with LC-MS and concentration-time data were analyzed using a noncompartmental approach. Absolute clearance (L/hr/kg) was significantly lower in men (0.039±0.017) than women (0.049±0.018;p=0.007) and in African Americans (0.039±0.017) when compared to Caucasians (0.048±0.018;p=0.019). Half-life was significantly longer in men than women as well as in African Americans when compared to Caucasians. The absolute bioavailability was 0.78. Sex and racial differences in clearance may contribute to variable dosing requirements and clinical response.