Effect of amlodipine on the pharmacokinetics of tacrolimus in rats

被引：12

作者：

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

Zhang, Bi-kui ^{[1
,2
]}

Li, Jing ^{[1
,3
]}

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

Yuan, Hong ^{[1
,2
]}

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

Cheng, Ze-neng ^{[2
]}

Liu, Zhi ^{[2
]}

Li, Pei-jiong ^{[2
]}

Tan, Hong-yi ^{[1
]}

Zhou, Ling-yun ^{[1
]}

Wang, Chung-jiang ^{[1
]}

Yang, Meng ^{[1
,2
]}

机构：

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

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

[3] Hunan Childrens Hosp, Dept Pharm, Changsha, Hunan, Peoples R China

来源：

XENOBIOTICA | 2013年 / 43卷 / 08期

基金：

中国国家自然科学基金; 国家教育部博士点专项基金资助;

关键词：

Amlodipine; CYP3A2; drug-drug interaction; P-glycoprotein; pharmacokinetics; tacrolimus; P-GLYCOPROTEIN; GRAPEFRUIT JUICE; CLINICAL PHARMACOKINETICS; CYTOCHROME-P450; 3A; METABOLISM; TRANSPORT; POLYMORPHISMS; HYPERTENSION; INHIBITION; DILTIAZEM;

D O I：

10.3109/00498254.2012.756992

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The immunosuppressant tacrolimus (TAC) is a substrate of cytochrome P450 3A2 (CYP3A2) and P-glycoprotein (P-gp) in rats. Amlodipine (AML) is an inhibitor of CYP3A2 in rats. We investigated the effect of AML on the pharmacokinetics of TAC in rats. 2. When co-administered with TAC orally or intravenously, AML decreased the oral clearance and raised the blood concentration of TAC in rats, but the T-1/2 of TAC was not significantly affected by AML. Upon oral administration of TAC, the effect of 15 mg/kg of AML on the AUC of TAC was lower than that seen with 5 or 10 mg/kg. However, upon intravenous TAC administration, the effect of 15 mg/kg of AML on the AUC of TAC was higher than that seen with 5 mg/kg. 3. AML is an inhibitor of P-gp and CYP3A2 in rats. If AML and TAC are co-administered orally, AML elicits greater inhibition in P-gp than CYP3A2 during first-pass metabolism. If AML is given orally and TAC given intravenously concurrently, AML mainly inhibits CYP3A2 activity and increases the blood concentration of TAC. There are significant pharmacokinetic interactions between TAC and AML. AML raises the blood concentration of TAC in rats probably by inhibiting P-gp and CYP3A2.

引用

页码：699 / 704

页数：6

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