Dose individualization is essential in
epilepsy treatment, especially in
antiepileptic drugs that present high interindividual variability such as
lamotrigine. We aimed an observational study to develop a population pharmacokinetic model for quantitative evaluation of the factors that influence
lamotrigine pharmacokinetics in Mexican adults with
epilepsy. Patients on stable treatment with
lamotrigine therapy were included, plasma concentrations were analyzed by a high-performance liquid chromatography method and UGT2B7-161C > T polymorphism was determined. The data were analyzed by NONMEM® 7.3, model validation was performed using bootstrap approach and visual predictive check. Finally, stochastic simulations were carried out to propose dosage regimens. A total of 73
lamotrigine plasma concentrations from 2 h after last dose and up to 0.5 h prior to next administration were fitted to a one-compartment open model. The final population pharmacokinetic model for
lamotrigine indicates that concomitant treatment with
valproic acid and
carbamazepine should be considered to individualize
epilepsy treatment with this drug. Based on this model, we proposed dosage regimens to achieve trough
lamotrigine concentrations within reference interval (2.5-15 mg/L). These results provide clinical useful data to give more rational
anticonvulsant therapy in our population.