Population Pharmacokinetics of Carbamazepine in Adults with Epilepsy

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.