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Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling
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
2009-12-01
DOI10.1007/s00228-009-0712-x
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
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51227
专题北京大学药学院
北京大学药学院_药剂学系
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
推荐引用方式
GB/T 7714
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.
APA Jiang, Dechun.,Bai, Xiangrong.,Zhang, Qingxia.,Lu, Wei.,Wang, Yuqin.,...&Mueller, Markus.(2009).Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling.EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY,65(12),1187-1193.
MLA Jiang, Dechun,et al."Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling".EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 65.12(2009):1187-1193.
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