Dosing Recommendations Based on Population Pharmacokinetics of Lamotrigine in Mexican Adult Patients With Epilepsy

• Published in: Journal of pharmaceutical sciences 2020-09, Vol.109 (9), p.2902-2908
• Main Authors: Chávez-Castillo, Cinthya Eloisa, Medellín-Garibay, Susanna Edith, Milán-Segovia, Rosa del Carmen, Rodríguez-Leyva, Ildefonso, Romano-Moreno, Silvia
• Format: Article
• Language: English
• Subjects: Clearance; Epilepsy; HPLC (high-performance/pressure liquid chromatography); Individualized drug therapy; Lamotrigine; Population pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2020.05.030

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.