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 (CI/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 (V(d)/F) (L) = 1.97 · total body weight; absorption rate constant (hr^-1) = 0.441. Interindividual variability in Cl/F and V(d)/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.