北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 期刊论文
学科主题: 药学
题名:
Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling
作者: Jiang, Dechun1,3,4; Bai, Xiangrong1; Zhang, Qingxia1; Lu, Wei2; Wang, Yuqin1; Li, Lin3; Mueller, Markus4
关键词: CYP2C19 ; CYP2C9 ; Genotype ; Valproic acid ; NONMEM ; Population pharmacokinetics
刊名: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
发表日期: 2009-12-01
DOI: 10.1007/s00228-009-0712-x
卷: 65, 期:12, 页:1187-1193
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: POPULATION PHARMACOKINETICS ; CYTOCHROME P4502C9 ; JAPANESE PATIENTS ; CLINICAL-DATA ; POLYMORPHISMS ; METABOLISM ; VALIDATION ; VOLUNTEERS ; MICROSOMES ; PHENYTOIN
英文摘要:

To evaluate the effects of CYP2C19 and CYP2C9 genotypes on the pharmacokinetic variability of valproic acid (VPA) in epileptic patients using a population pharmacokinetic (PPK) approach.

VPA concentrations were measured in 287 epileptic patients, who were genotyped for CYP2C19*2/*3 and CYP2C9*3. Patients who were on monotherapy with VPA were divided into two groups, a PPK-model group (n = 177) and a PPK-valid group (n = 110). The PPK parameter values for VPA were calculated in the PPK-model group by using the NONMEM software. Ultimately, a biological model and a final model were established. Each model was then used to independently predict the concentrations of the PPK-valid group to validate the two models.

There was a significant effect of the CYP2C19 and CYP2C9 genotypes on the pharmacokinetic (PK) variability (P < 0.01) in the final PPK model of CL/F. The interindividual CL was calculated according to the final model: CL/F = 0.0951 x (1 + e(0.0267 x (3 -aEuro parts per thousand genotype))) + 0.0071 x age (L/h). The coefficient of variation (CV) (omega CL/F) of the final model was 29.3%, while that of the biological model was 31.7%. Based on the genotype, the individual PK parameters can be calculated more accurately than before.

The CYP2C19 and CYP2C9 genotypes significantly influenced the PK variability of VPA, as quantified by NONMEM software.

语种: 英语
WOS记录号: WOS:000271949400004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51227
Appears in Collections:北京大学药学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Capital Med Univ, Dept Pharm, Xuanwu Hosp, Beijing 100053, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
3.Capital Med Univ, Dept Pharmacol, Educ Minist, Key Lab Neurodegenerat Dis,Xuanwu Hosp, Beijing 100053, Peoples R China
4.Vienna Med Univ, Dept Clin Pharmacol, A-1090 Vienna, Austria

Recommended Citation:
Jiang, Dechun,Bai, Xiangrong,Zhang, Qingxia,et al. Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling[J]. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY,2009,65(12):1187-1193.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Jiang, Dechun]'s Articles
[Bai, Xiangrong]'s Articles
[Zhang, Qingxia]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Jiang, Dechun]‘s Articles
[Bai, Xiangrong]‘s Articles
[Zhang, Qingxia]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace