POPULATION PHARMACOKINETICS OF CARBAMAZEPINE IN ADULTS WITH EPILEPSY

Study Objective. To conduct a population pharmacokinetic analysis of c arbamazepine (CBZ). Design. Retrospective chart review. Setting. Ambul atory neurology clinics at three medical centers. Patients. Patients d iagnosed with epilepsy from 1991-1995. The index set included 829 adul ts receiving CBZ. A separate validation set consisted of SO patients. Interventions. None. Measurements and Main Results. Final regression e quations were apparent oral clearance (Cl/F) (L/hr) = (0.0134 .TEW + 3 .58), .1.42 if receiving phenytoin only; .1.17 if receiving phenobarbi tal or felbamate; . 1.62 if receiving phenytoin and phenobarbital or f elbamate; . 0.749 if age greater than or equal to 70 years; apparent v olume of distribution (V-d/F) (L) = 1.97 . total body weight; absorpti on 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 m g/L. Conclusions. These routinely collected data provided quantitative estimates of changes in CBZ Cl/F due to comedication and an age-relat ed decrease in Cl/F The derived regression equations reasonably predic ted concentrations in a separate validation set.