Lamotrigine pharmacokinetic evaluation in epileptic patients submitted to VEEG monitoring

Abstract

Objective: The aim of the present study was to evaluate the pharmacokinetic profile of lamotrigine (LTG) in epileptic patients submitted to video-electroencephalography (VEEG) monitoring and, in addition, to investigate the influence of concomitant antiepileptic drugs (AEDs) on the kinetics of LTG. Methods: The analysis assumed a one-compartment open model with first-order absorption and elimination. The kinetic estimates obtained in this population were validated by using the Prediction- Error approach. The influence of medication was also assessed by the calculation of the LTG concentration-todose ratio. Patients (n=135) were divided into four groups according to the co-medication: Group 1, patients taking LTG with enzyme-inducer agents; Group 2, patients receiving LTG with valproic acid; Group 3, patients receiving both inducers and inhibitors of LTG metabolism; Group 4, patients under AEDs not known to alter LTG metabolism. Results: The obtained estimates for clearance (CL) (L/h/kg) [0.075±0.029 (Group 1), 0.014±0.005 (Group 2), 0.025±0.008 (Group 3) and 0.044±0.011 (Group 4)] appear to be the most appropriate set to be implemented in clinical practice as prior information, as demonstrated by the accuracy and precision of the measurements. In addition, the influence of co-medication on the LTG profile was further confirmed by the basal LTG concentration-to-dose ratio. Conclusion: The results of the present investigation may contribute to achieving the goal of optimizing patients’ clinical outcomes by managing their medication regimen through measured drug concentrations. Patients submitted to VEEG monitoring may benefit from this study, as the results may be used to provide better drug management in this medical setting.