Predictive capacity of carbamazepine pharmacokinetic parameters in a Portuguese outpatient population

The individualization of anticonvulsant therapy regimens can contribute to the implementation of appropriate carbamazepine (CBZ) maintenance doses in epileptic patients. An accurate method for thr prediction of concentrations based on a determination of parameters and serum concentrations could be o f clinical relevance in the management of epilepsy. In this study, we retro spectively evaluated the predictive performance in an adult outpatient popu lation of six different methods! representing six sets of CBZ pharmacokinet ic parameters selected according to the literature using a Bayesian compute r program (PKS System; Abbott Laboratories, Abbott Park, IL, USA). The stud y involved 50 patients with two or more available concentrations selected u nder 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 concentrat ions. Accuracy and precision were assessed by mean prediction error (ME), m ean squared prediction error (MSE) and mot mean squared prediction error (R MSE). The analysis showed CL = 0.067 L/hour/kg and V-d = 1.19 L/kg as the m ost accurate and precise set of pharmacokinetic parameters, presenting the highest percentage of clinically acceptable estimates (error < 2 mu g/mL). Additionally, predictions based on one measured feedback concentration were found to be more accurate and precise than prior population-based predicti ons; the use of two previous patient concentrations further improved predic tive capacity but failed to show a significant difference when compared wit h predictions based on one measured feedback concentration. In conclusion, the adoption of the previously mentioned set of parameters as population es timates and the use of at least one feedback concentration through the Baye sian approach seems to be essential for a better CBZ use in clinical practi ce. Finally, despite the obtained results, we believe that the Portuguese p harmacokinetic parameter determination of antiepileptics should be carried out to improve the rationale and cost-effectiveness of anticonvulsant thera py.