Abstract
PURPOSE: We aimed to evaluate the effect of the ABCC2 1249G>A (rs2273697) and -24C>T (rs717620) polymorphisms on lacosamide (LCM) plasma concentrations and the efficacy of LCM in Uygur pediatric patients with epilepsy. METHODS: We analyzed 231 pediatric patients with epilepsy, among which 166 were considered to be LCM responsive. For drug assays, 2-3 mL of venous blood was collected from each patient just before the morning LCM dose was administered (approximately 12 hours after the evening dose, steady-state LCM concentrations). The remaining samples after routine therapeutic drug monitoring were used for genotyping analysis. The χ 2 test and Fisher exact test were utilized for comparative analysis of the allelic and genotypic distribution of ABCC2 polymorphisms between the LCM-resistant and LCM-responsive groups. The Student t test or Mann-Whitney U test was conducted to analyze differences in plasma LCM concentration among pediatric patients with epilepsy with different genotypes. RESULTS: Patients with the ABCC2 1249G>A GA genotype (0.7 ± 0.3 mcg/mL per kg/mg) and AA genotype (0.5 ± 0.3 mcg/mL per kg/mg) showed significantly ( P < 0.001) lower LCM concentration-to-dose (CD) ratios than patients with the GG genotype (1.0 ± 0.4 mcg/mL per kg/mg). Moreover, patients with the ABCC2 -24C>T CT genotype (0.6 ± 0.2 mcg/mL per kg/mg) and TT genotype (0.6 ± 0.3 mcg/mL per kg/mg) presented a significantly ( P < 0.001) lower LCM CD ratio than patients with the CC genotype (1.1 ± 0.4 mcg/mL per kg/mg). CONCLUSIONS: The ABCC2 1249G>A (rs2273697) and ABCC2 -24C>T (rs717620) polymorphisms can affect plasma LCM concentrations and treatment efficacy among a population of Uygur pediatric patients with epilepsy, causing these patients to become resistant to LCM. In clinical practice, ABCC2 polymorphisms should be identified before LCM treatment, and then, the dosage should be adjusted for pediatric patients with epilepsy accordingly.