A Population Pharmacokinetic-Pharmacogenetic Model of Lamotrigine in Chinese Children With Epilepsy

Therapeutic Drug Monitoring
Yanan ChenLimei Zhao

Abstract

The pharmacokinetics of lamotrigine (LTG) is complex and varies significantly among individuals, especially among children. Therefore, this study aimed to establish a population pharmacokinetic (PPK) model of LTG in Chinese children with epilepsy and to comprehensively evaluate the effects of genetic variations in drug-metabolizing enzymes, transporters, and a transcriptional regulator on LTG pharmacokinetics. Three hundred eighty-five steady-state plasma concentrations were obtained from 179 children (age 10.72 ± 3.05 years and body weight 46.23 ± 17.77 kg) with epilepsy during therapeutic drug monitoring. These patients were divided into the PPK-model group (n = 121) and the PPK-validation group (n = 58) and were genotyped for UGT1A4, UGT2B7, ABCB1, ABCG2, SLC22A1, and HNF4α. PPK analysis was performed by nonlinear mixed effects modeling. In the final model, apparent clearance (CL/F) of LTG was estimated to be 1.48 L/h; 500 mg valproic acid, oxcarbazepine, and UGT2B7-161TT genotype changed the CL/F by -46.2, +31.1, and -21.8%, respectively. Body weight was also identified as a significant covariate affecting LTG CL/F. A PPK-pharmacogenetic model of LTG in Chinese children with epilepsy was successfully established with nonlin...Continue Reading

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Citations

May 3, 2020·International Journal of Molecular Sciences·Ramon Cacabelos
Jul 23, 2020·Therapeutic Drug Monitoring·José Eduardo Juárez-HernándezGilberto Castañeda-Hernández
Apr 16, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ming-Lu WangLimei Zhao
Oct 17, 2020·Seizure : the Journal of the British Epilepsy Association·Janthima Methaneethorn, Nattawut Leelakanok

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