Effect of CYP3A5*3 Polymorphism on Pharmacokinetic Drug Interaction between Tacrolimus and Amlodipine

被引：38

作者：

Zuo, Xiao-cong ^{[1
,2
]}

Zhou, Ya-nan ^{[1
,2
]}

Zhang, Bi-kui ^{[1
,3
]}

Yang, Guo-ping ^{[1
,2
]}

Cheng, Ze-neng ^{[2
]}

Yuan, Hong ^{[1
,2
]}

Ouyang, Dong-sheng ^{[2
]}

Liu, Shi-kun ^{[1
,2
]}

Barrett, Jeffrey S. ^{[3
]}

Li, Pei-jiong ^{[2
]}

Liu, Zhi ^{[2
]}

Tan, Hong-yi ^{[1
]}

Guo, Ren ^{[1
]}

Zhou, Ling-yun ^{[1
]}

Xie, Yue-liang ^{[1
]}

Li, Zuo-jun ^{[1
]}

Li, Jing ^{[2
]}

Wang, Chun-jiang ^{[1
]}

Wang, Jiang-lin ^{[1
,2
]}

机构：

[1] Cent S Univ, Xiangya Hosp 3, Clin Pharm & Pharmacol Res Inst, Changsha 410013, Hunan, Peoples R China

[2] Cent S Univ, Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China

[3] Childrens Hosp Philadelphia, Clin Pharmacol & Therapeut Div, Lab Appl PK PD, Philadelphia, PA 19104 USA

来源：

DRUG METABOLISM AND PHARMACOKINETICS | 2013年 / 28卷 / 05期

基金：

中国国家自然科学基金;

关键词：

tacrolimus; amlodipine; pharmacokinetics; CYP3A5*3 polymorphism; drug-drug interaction; RENAL-TRANSPLANT PATIENTS; CALCIUM-CHANNEL BLOCKERS; POPULATION PHARMACOKINETICS; CLINICAL PHARMACOKINETICS; GENETIC-POLYMORPHISMS; ORGAN-TRANSPLANTATION; DOSE REQUIREMENTS; CYP3A5; GENOTYPES; HEART-TRANSPLANT; CYCLOSPORINE-A;

D O I：

10.2133/dmpk.DMPK-12-RG-148

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The objective of this study was to evaluate the effect of the CYP3A5*3 allele on the pharmacokinetics of tacrolimus and amlodipine, and drug-drug interactions between them in healthy subjects. Pharmacokinetic drug interactions between tacrolimus and amlodipine were evaluated in a randomized, 3-period, 6-sequence crossover study in healthy Chinese volunteers according to CYP3A5 genotype. A single-dose and multiple-dose study were designed. A 96-h pharmacokinetic study followed either tacrolimus or amlodipine dose, and the washout periods between the study phases were 14 days. In the single-dose study, apparent oral clearance (CL/F) of tacrolimus (5 mg) in CYP3A5 expressers was 3.8-fold (p=0.008) higher than that in CYP3A5 non-expressers. Amlodipine decreased mean tacrolimus CL/F in CYP3A5 expressers by 2.2-fold (p=0.005), while it had no effect on that in CYP3A5 non-expressers. The CL/F of amlodipine in CYP3A5 non-expressers was 2.0-fold (p=0.001) higher than that in CYP3A5 expressers. Tacrolimus increased mean amlodipine CL/F in CYP3A5 expressers by 1.4-fold (p=0.016) while it had no effect on that in CYP3A5 non-expressers. Tacrolimus slightly reduced the AUC(0-infinity). of amlodipine in both CYP3A5 expressers and non-expressers. Dose adjustment of tacrolimus should be considered according to CYP3A5*3 genetic polymorphism when tacrolimus is coadministered with amlodipine.

引用

页码：398 / 405

页数：8

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