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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.
- Source :
-
European journal of clinical pharmacology [Eur J Clin Pharmacol] 2015 Nov; Vol. 71 (11), pp. 1341-7. Date of Electronic Publication: 2015 Aug 26. - Publication Year :
- 2015
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adolescent
Anticonvulsants blood
Asian People genetics
Child
Child, Preschool
Drug Therapy, Combination
Epilepsy blood
Epilepsy drug therapy
Female
Genotype
Humans
Lamotrigine
Male
Polymorphism, Single Nucleotide
Triazines blood
Anticonvulsants pharmacokinetics
Anticonvulsants pharmacology
Epilepsy genetics
Glucuronosyltransferase genetics
Triazines pharmacokinetics
Valproic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1041
- Volume :
- 71
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- European journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26303110
- Full Text :
- https://doi.org/10.1007/s00228-015-1925-9