The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects

doi:10.1007/s00228-009-0736-2

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	The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects
	Tan, Bo 1; Zhang, Yi-Fan1 ; Chen, Xiao-Yan1 ; Zhao, Xiao-Hua 1; Li, Guo-Xin 2; Zhong, Da-Fang1
刊名	EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
	2010-02
卷号	66 期号:2 页码:145-151
关键词	Glipizide CYP2C9 CYP2C19 Genetic polymorphism Pharmacokinetics Pharmacodynamics
ISSN号	0031-6970
DOI	10.1007/s00228-009-0736-2
文献子类	Article
英文摘要	Objective To study the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide. Methods Eighteen healthy male subjects were divided into three groups according to their genotypes: group I, CYP2C91/1 and CYP2C19 extensive metabolizers (EMs); group II, CYP2C91/1 and CYP2C19 poor metabolizers (PMs); and group III, CYP2C91/3 and CYP2C19 EMs. After a single dose of a 5-mg glipizide tablet, plasma concentrations of glipizide for a 36-h period were determined. Meanwhile, plasma glucose levels and plasma insulin levels were determined from 0 to 4 h after dosing. Results The area under the plasma concentration-time curve (AUC(0-infinity)) was 2.0-fold higher and the oral clearance was 51.1% lower in group III than in group I. The change in fasting insulin level within 1 h (Delta AUEC(insulin0-1h)) in group III was 3.8-fold higher than that in group I. The glipizide parameters in group II exhibited similar tendencies to those in group III. Conclusions These results suggest that CYP2C9 polymorphism significantly influences the pharmacokinetics and pharmacodynamics of glipizide, which needs to be considered in clinical practice. CYP2C19 polymorphism exhibits a tendency to influence the effects of glipizide, to a certain extent similarly to CYP2C9 polymorphism.
资助项目	Natural Science Foundation of China[30772621]
WOS关键词	METABOLISM ; GLIBENCLAMIDE ; GENOTYPE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER HEIDELBERG
WOS记录号	WOS:000274022300005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278981]
专题	上海药物代谢研究中心
通讯作者	Zhong, Da-Fang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Liaoning Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Clin Pharmacol, Shenyang 110034, Peoples R China
推荐引用方式 GB/T 7714	Tan, Bo,Zhang, Yi-Fan,Chen, Xiao-Yan,et al. The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects[J]. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY,2010,66(2):145-151.
APA	Tan, Bo,Zhang, Yi-Fan,Chen, Xiao-Yan,Zhao, Xiao-Hua,Li, Guo-Xin,&Zhong, Da-Fang.(2010).The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects.EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY,66(2),145-151.
MLA	Tan, Bo,et al."The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects".EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 66.2(2010):145-151.