中国药业2016，Vol.25Issue(16)：63-66,4.
细胞色素P4503A5和细胞色素P4502C19基因多态性对伏立康唑药代动力学的影响
Influence of Gene Polymorphisms of Cytochrome P4503A5 and Cytochrome P4502C19 on the Pharmacokinetics of Voriconazole
黄金梅 1陈桂香 2李志平 1袁娇1
作者信息
- 1. 广东省东莞市第五人民医院，广东 东莞 523900
- 2. 广东省东莞市中医院，广东 东莞 523125
- 折叠
摘要
Abstract
Objective To analyze the influence of gene PolymorPhism of cytochrome P4503A5(CYP3A5)and CYP2C19 on the Pharma-cokinetics of voriconazole. Methods By RFLP-PCR method,CYP3A5,CYP2C19 whole blood genotyPing was carried out on 20 healthy male volunteers. All volunteers took a single oral dose of voriconazole tablets 200 mg,and the liquid chromatograPhy- tandem mass sPectrometry (LC-MS) of Plasma concentrations of volunteers at various Points was determined,and DAS 2. 0 software was used for calculating the Pharmacokinetic Parameters of drugs. Main effects model was used with a seParate analysis on the half-life Period( t1/2), the aPParent clearance( CL/ F),Peak Plasma concentration( Cmax),area under the curve at 0~36 h drug( AUC0 -36)and The total area under the curve ( AUC0 -∞) of CYP3A5 and CYP2C19. Results Different CYP3A5 genotyPes showed no significantly difference in Pharmacokinetic Parameters of voriconazole ( P > 0. 05);different CYP2C19 genotyPes showed no significant difference on t1 /2,Cmax ( P > 0. 05),while CL/ F,AUC0-36 and AUC0 -∞ showed significant differences ( P < 0. 05);multiPle comParison method on CL/ F, AUC0 - 36,AUC0 - ∞ Scheffe of CYP2C19 showed,AUC0 - 36 and AUC0 - ∞ values of CYP2C19 mutations were significantly higher than homozygous wild grouP and heterozygous mutation grouP ( P < 0. 05),while CL/ F value of CYP2C19 mutant homozygotes was significantly lower than wild grouP ( P < 0. 05). Conclusion Gene PolymorPhism of CYP2C19 has a significant effect on voriconazole Pharmacokinetic Process;while gene PolymorPhism of CYP3A5 has no obvious influence on voriconazole Pharmacokinetic Process.关键词
细胞色素P4503A5/细胞色素P4502C19/基因多态性/伏立康唑/药代动力学Key words
cytochrome P4503A5/cytochrome P4502C19/gene PolymorPhism/voriconazole/Pharmacokinetics分类
医药卫生引用本文复制引用
黄金梅,陈桂香,李志平,袁娇..细胞色素P4503A5和细胞色素P4502C19基因多态性对伏立康唑药代动力学的影响[J].中国药业,2016,25(16):63-66,4.
