Predictive capacity of carbamazepine pharmacokinetic parameters in a Portuguese outpatient population.

Abstract

The individualization of anticonvulsant therapy regimens can contribute to the implementation of appropriate carbamazepine (CBZ) maintenance doses in epileptic patients. An accurate method for the prediction of concentrations based on a determination of parameters and serum concentrations could be of clinical relevance in the management of epilepsy. In this study, we retrospectively evaluated the predictive performance in an adult outpatient population of six different methods, representing six sets of CBZ pharmacokinetic parameters selected according to the literature using a Bayesian computer program (PKS System; Abbott Laboratories, Abbott Park, IL, USA). The study involved 50 patients with two or more available concentrations selected under several inclusion criteria. The patients were taking CBZ (between 200 and 1600 mg/d) in monotherapy or polytherapy regimens and had no hepatic or renal disease. Steady state concentrations were predicted according to the use of prior information and using one and two feedback patient concentrations. Accuracy and precision were assessed by mean prediction error (ME), mean squared prediction error (MSE) and root mean squared prediction error (RMSE). The analysis showed CL = 0.067 L/hour/kg and Vd = 1.19 L/kg as the most accurate and precise set of pharmacokinetic parameters, presenting the highest percentage of clinically acceptable estimates (error < 2 microg/mL). Additionally, predictions based on one measured feedback concentration were found to be more accurate and precise than prior population-based predictions; the use of two previous patient concentrations further improved predictive capacity but failed to show a significant difference when compared with predictions based on one measured feedback concentration. In conclusion, the adoption of the previously mentioned set of parameters as population estimates and the use of at least one feedback concentration through the Bayesian approach seems to be essential for a better CBZ use in clinical practice. Finally, despite the obtained results, we believe that the Portuguese pharmacokinetic parameter determination of antiepileptics should be carried out to improve the rationale and cost-effectiveness of anticonvulsant therapy.