当前位置： SCI文献检索 > EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Influence of valproic acid concentration and polymorphism of UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2 on serum concentration of lamotrigine in Chinese epileptic children.

Influence of valproic acid concentration and polymorphism of UGT1A43, UGT2B7 -161C > T and UGT2B72 on serum concentration of lamotrigine in Chinese epileptic children.

Abstract：

PURPOSE:To investigate the impact of valproic acid (VPA) and genetic polymorphism of the major metabolizing enzyme (UGT1A4, UGT2B7) of lamotrigine (LTG) and VPA on LTG concentration in Chinese epileptic children. METHODS:Three single nucleotide polymorphisms (UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2) were analyzed by polymerase chain reaction-restriction fragment length polymorphism or direct DNA sequencing. The concentrations of LTG and VPA were measured by high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay, respectively. The adjusted concentration of LTG was defined as the concentration-to-dose-ratio (CDRLTG). Data analysis was performed using IBM SPSS Statistics 21.0. RESULTS:A total of 56 patients treated with LTG as monotherapy and 158 patients treated with LTG plus VPA were included in this study. In the polytherapy group, LTG concentration showed a good linear relationship with gender, age, daily LTG dose, VPA concentration, and UGT1A4*3 polymorphism, but had no relationship with the polymorphism of UGT2B7 -161C > T or UGT2B7*2. Moreover, LTG concentration and CDRLTG for the UGT1A4*3 were higher compared to UGT1A4*1 (LTG: 7.24 ± 3.51 vs 5.26 ± 3.27 μg/mL, p = 0.001; CDRLTG: 2.75 ± 1.02 vs 2.14 ± 0.96 μg/mL per mg/kg, p < 0.001, respectively). In the monotherapy group, there was no statistical difference between UGT1A4*3 and UGT1A4*1 in LTG concentration or CDRLTG. The patients in the polytherapy group were divided into two subgroups according to VPA concentration (lower/higher: 10-50/50-125 μg/mL). CDRLTG values of the patients carrying the UGT1A4*3 genotype were higher compared to UGT1A4*1*1 (2.86 ± 1.03 vs 2.22 ± 0.94 μg/mL per mg/kg, p = 0.001) only when the VPA concentration was higher. CONCLUSIONS:UGT1A4*3 polymorphism had an effect on LTG concentration only with VPA co-administration, and the effect was remarkable when VPA concentration was higher.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Liu L,Zhao L,Wang Q,Qiu F,Wu X,Ma Y

doi

10.1007/s00228-015-1925-9

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

1341-7

issue

eissn

0031-6970

issn

1432-1041

pii

10.1007/s00228-015-1925-9

journal_volume

pub_type

临床试验,杂志文章

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Influence of valproic acid concentration and polymorphism of UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2 on serum concentration of lamotrigine in Chinese epileptic children.

Influence of valproic acid concentration and polymorphism of UGT1A43, UGT2B7 -161C > T and UGT2B72 on serum concentration of lamotrigine in Chinese epileptic children.