Effects of cytochrome P450 isozymes 2A6, 2B6, 2C9 and 2C19 genetic polymorphisms on plasma concentration of sodium valproate
10.3760/cma.j.issn.1006-7876.2013.02.004
- VernacularTitle:细胞色素P450酶2A6、2B6、2C9及2C19基因多态性对丙戊酸钠血药浓度的影响
- Author:
Qingchuan LIAO
;
Jingjing SHI
;
Yong ZHANG
;
Xiaolei LI
;
Siting LIU
;
Jinchun QIU
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Valproic acid;
Plasma concentration;
Aryl hydrocarbon hydroxylases;
Oxidoreductases,N-demethylating;
Polymorphism,genetic
- From:
Chinese Journal of Neurology
2013;(2):82-86
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the influences of the functional polymorphisms of cytochrome P450 isozymes 2A6 (CYP2A6),2B6 (CYP2B6),2C9 (CYP2C9),and 2C19 (CYP2C19) on plasma concentration of sodium valproate.Methods A total of 131 Chinese children with epilepsy receiving sodium valproate after a period of more than 5 half-time were recruited.The genotypes of CYP2A6 were detected by multiplex polymerase chain reaction (PCR),and the genotypes of CYP2B6,CYP2C9,and CYP2C19 were detected by PCR-ligase detection reaction.Enzyme-multiplied immunoassay technique was used to measure the plasma concentration of sodium valproate.The association between the polymorphisms and the plasma concentration of sodium valproate were analyzed by one-way ANOVA or Student' s t-test.Results Patients were divided into 4 groups according to the genotyping results of CYP2C9 and CYP2C19 (G1:extensive metabolizers in both CYP2C9 and CYP2C19; G2:CYP2C19 intermediate metabolizers; G3:CYP2C19 poor metabolizers; G4:CYP2C9 poor metabolizers),the mean normalized steady-state sodium valproate concentrations were significantly higher in G3 (3.70 ± 0.95) and G4 (4.35 ± 1.48) patients when compared to those in G 1 (2.57 ± 1.30,t =3.056,4.490,both P ＜ 0.01) and G2 (2.76 ± 1.19,t =2.827,4.462,both P ＜ 0.01) patients.The daily doses (mg/d) of sodium valproate received by G3 (19.46 ± 5.20) and G4 (19.30 ±7.67) patients were significantly lower than that of G1 patients(24.10 ±6.97,t =2.359,2.297,both P ＜ 0.05).There were no differences in daily doses or normalized steady-state concentrations of sodium valproate among the CYP2A6* 4 or CYP2B6* 6 genotypic groups.Conclusions The CYP2C9 and CYP2C19 polymorphisms have dramatic effects on the plasma concentration of sodium valproate.The daily doses of sodium valproate in G3 and G4 patients should be lower than usual.
