Postinduction carbamazepine clearance in an adult psychiatric population

The objective of this study was to describe the postinduction clearance of carbamazepine (CBZ) in adult psychiatric patients by population pharmacokinetic analysis using the NONMEM program. Specifically, an estimate of CBZ clearance and insight into the effect of common patient characteristics on clearance were sought. Steady-state trough CBZ serum concentrations, CBZ dosing history, concomitant drug administration, and other data from 45 patients were collected retrospectively. A one-compartment model with first-order absorption and first-order elimination was used, with absorption rate, bioavailability, and volume of distribution fixed to literature values. No evidence was found that race, sex, age, ethanol use, smoking, and concomitant lithium significantly affected CBZ clearance. In the final model, clearance was based on lean body weight. The coefficient of variation for clearance estimates was 16.5%. Residual variability was modest. Estimates for volume of distribution, rates of absorption and elimination, and bioavailability could not be pursued rigorously. Although these results may assist in understanding CBZ disposition in this population, their general clinical application should be approached with caution.