A total of 73 adults patients on stable treatment with LTG at least two weeks as mono or adjunctive therapy attended at the Epilepsy Clinic of the Hospital Central “Dr. Ignacio Morones Prieto” were included. LTG was determined by HPLC-UV technique in one plasma sample per patient. Population pharmacokinetics analysis was performed by non-linear mixed effects modelling approach using NONMEM® software. The covariables tested were: age, sex, height, weight, serum albumin, creatinine, alanine transaminase, and aspartate aminotransferase levels, creatinine clearance, body mass index, body surface, tobacco consumption, UGT2B7 genetic variants, comorbidities and adjunctive therapy.

Absorption rate constant, bioavailability and distribution volume were fixed at 1.4 h^-1, 1.00 and 1.8 L/kg, respectively, to stabilize the model. LTG clearance was estimated at 1.82 Lh^-1 and was associated with co-treatment with valproic acid (VPA) and carbamazepine (CBZ). The final population pharmacokinetic model for LTG was CL (L/h) = 1.82 x (1 - 0.465 VPA) x (1 + 0.841 CBZ) and it explains 23% of the interindividual variability associated with LTG clearance. This model was internally validated by bootstrap and visual predictive check techniques. Stochastic simulations were performed to propose dosage regimens considering comedication with VPA and CBZ to achieve reference interval (2.5 – 15 mg/L).

This is the first population pharmacokinetic study of LTG in Mexican patients and indicates that co-treatment with VPA and CBZ should be considered to individualize epilepsy treatment with this drug.