Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects

doi:10.1111/j.1365-2125.2007.02846.x

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 上海药物代谢研究中心

	Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects
	Zhang, Yifan; Si, Dayong ; Chen, Xiaoyan; Lin, Nan ; Guo, Yingjie ; Zhou, Hui ; Zhong, Dafang
刊名	BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
	2007-07
卷号	64 期号:1 页码:67-74
关键词	clinical pharmacokinetics CYP2C19 CYP2C9 gliclazide polymorphism
ISSN号	0306-5251
DOI	10.1111/j.1365-2125.2007.02846.x
文献子类	Article
英文摘要	Aims To investigate the influence of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics of gliclazide modified release (MR) in healthy Chinese subjects. Methods In a single-dose pharmacokinetic study, 24 healthy male subjects with various CYP2C9 and CYP2C19 genotypes received an oral dose of 30 mg gliclazide MR and plasma was sampled for 72 h postdose. In a multiple-dose pharmacokinetic study, 17 other CYP2C91 homozygotes with various CYP2C19 genotypes received 30 mg gliclazide MR once daily for 6 days and plasma was sampled after the last dose. The plasma concentrations of gliclazide were measured using a validated LC/MS/MS method. CYP2C9 and CYP2C19 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Results In the single-dose study, no significant difference in any pharmacokinetic parameters was found in CYP2C91/1, 1/3 and 1/13 subjects. In contrast, the AUC(0-infinity) of gliclazide was significantly increased by 3.4-fold [95% confidence interval (CI) 2.5, 4.7; P < 0.01] in CYP2C19 poor metabolizer (PM) subjects compared with CYP2C191 homozygotes. The half-life (t(1/2)) was prolonged from 15.1 to 44.5 h (P < 0.01). Similar differences were found in the multiple-dose study. The parameters of gliclazide AUC(ss), AUC(0-infinity) and C-max were 3.4-fold (95% CI 2.9, 4.0), 4.5-fold (95% CI 3.8, 5.4) and 2.9-fold (95% CI 2.4, 3.4) increased (P < 0.01) in CYP2C19 PM subjects, respectively, compared with CYP2C19*1 homozygotes, and t(1/2) was increased from 13.5 to 24.6 h (P < 0.01). Conclusions The pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism.
WOS关键词	MODIFIED RELEASE ; CYTOCHROME P4502C9 ; HEALTHY-VOLUNTEERS ; GENOTYPE ; PHARMACODYNAMICS ; HYDROXYLATION ; FREQUENCIES ; LORNOXICAM ; METABOLISM ; PHENOTYPE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	BLACKWELL PUBLISHING
WOS记录号	WOS:000247318800008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273208]
专题	上海药物代谢研究中心
通讯作者	Zhong, Dafang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Jilin Univ, Coll Life Sci, Changchun 130023, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Yifan,Si, Dayong,Chen, Xiaoyan,et al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects[J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,2007,64(1):67-74.
APA	Zhang, Yifan.,Si, Dayong.,Chen, Xiaoyan.,Lin, Nan.,Guo, Yingjie.,...&Zhong, Dafang.(2007).Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects.BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,64(1),67-74.
MLA	Zhang, Yifan,et al."Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects".BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 64.1(2007):67-74.