Population Pharmacokinetics of Carbamazepine in Adults with Epilepsy

Abstract

Study Objective. To conduct a population pharmacokinetic analysis of carbamazepine (CBZ).Design. Retrospective chart review.Setting. Ambulatory neurology clinics at three medical centers.Patients. Patients diagnosed with epilepsy from 1991–1995. The index set included 829 adults receiving CBZ. A separate validation set consisted of 50 patients.Interventions. None.Measurements and Main Results. Final regression equations were apparent oral clearance (Cl/F) (L/hr) = (0.0134 • TBW + 3.58), • 1.42 if receiving phenytoin only; • 1.17 if receiving phenobarbital or felbamate; • 1.62 if receiving phenytoin and phenobarbital or felbamate; • 0.749 if age ≥ 70 years; apparent volume of distribution (Vd/F) (L) = 1.97 • total body weight; absorption rate constant (hr−1) = 0.441. Interindividual variability in Cl/F and Vd/F was 26% and 82%, respectively. Residual variability was 1.8 mg/L. Predictive performance analysis of the validation set provided a mean prediction error of 0.6 mg/L and median absolute error of 2.4 mg/L.Conclusions. These routinely collected data provided quantitative estimates of changes in CBZ Cl/F due to comedication and an age‐related decrease in Cl/E The derived regression equations reasonably predicted concentrations in a separate validation set.