机构：[a]Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China[b]Department of Pharmacy, Guangdong Provincial Traditional Chinese Medical Hospital, Guangzhou 510080, China[c]Department of Neurology, Epilepsy Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China中山大学附属第一医院[d]Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA[e]Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510006, China
Lamotrigine (LTG) is commonly used to control seizure in epilepsy patients and with referenced therapeutic windows in clinical practice. This study is to identify and characterize the function of genetic variants that influence the trough concentrations of LTG in epilepsy patients following monotherapy regimen (37.5-250 mg/d). Twelve single nucleotide polymorphisms (SNPs) involved in LTG metabolism and transport pathways, including UGT2B7, ABCB1, ABCG2, NR1I2 and HNF4 alpha were genotyped in 140 Chinese epilepsy patients. Steady-state trough concentration of LTG was measured by a high-performance liquid chromatography method. Polymorphisms in ABCG2 rs2231142, rs3114020, HNF4 alpha rs2071197 and ABCB1 rs1128503 were found to be associated with LTG CDR (concentration/dose normalized by body weight). In addition, multiple linear regression analysis revealed that ABCG2 rs2231142 had a remarkable effect on LTG concentrations which is stated to be 4.8% of the variability of LTG and may also help to interpret ethnic difference in LTG pharmacokinetics. Our findings provided new insights that SNPs of genes involved in the transport of LTG contribute to interpatient variation in LTG pharmacokinetics. Future studies are necessary to determine whether these SNPs can be used to provide LTG dosing guidance and influence seizure control and adverse reaction of LTG. Copyright (C) 2015, Published by Elsevier Ltd on behalf of The Japanese Society for the Study of Xenobiotics.
基金：
This work was supported by the Natural Major Projects for science
and technology development from Science and Technology
Ministry of China (Grant No. 2012ZX09506001-004) and the National
Natural Science Foundation of China (Grant No.
81320108027, 81173131, 81473283).
第一作者机构：[a]Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Yafang Zhou,Xueding Wang,Hongliang Li,et al.Polymorphisms of ABCG2, ABCB1 and HNF4 alpha are associated with Lamotrigine trough concentrations in epilepsy patients[J].DRUG METABOLISM AND PHARMACOKINETICS.2015,30(4):282-287.doi:10.1016/j.dmpk.2015.05.002.
APA：
Yafang Zhou,Xueding Wang,Hongliang Li,Jie Zhang,Ziyi Chen...&Min Huang.(2015).Polymorphisms of ABCG2, ABCB1 and HNF4 alpha are associated with Lamotrigine trough concentrations in epilepsy patients.DRUG METABOLISM AND PHARMACOKINETICS,30,(4)
MLA：
Yafang Zhou,et al."Polymorphisms of ABCG2, ABCB1 and HNF4 alpha are associated with Lamotrigine trough concentrations in epilepsy patients".DRUG METABOLISM AND PHARMACOKINETICS 30..4(2015):282-287
