期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 28, 期 5, 页码 398-405出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.DMPK-12-RG-148
关键词
tacrolimus; amlodipine; pharmacokinetics; CYP3A5*3 polymorphism; drug-drug interaction
资金
- National Natural Science Foundation of China [81102512, 81273594]
- National Basic Research Program of China [2011CB512001]
- Ministry of Education of China [20110162120023, 20100162110049]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据