title: Effect of amlodipine on the pharmacokinetics of tacrolimus in rats.
abstract: 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 T1/2 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.
authors: Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha, China.
authors: Ya-nan
authors: YN
authors: Zhou
authors: Bi-kui
authors: BK
authors: Zhang
authors: Jing
authors: J
authors: Li
authors: Xiao-cong
authors: XC
authors: Zuo
authors: Hong
authors: H
authors: Yuan
authors: Guo-ping
authors: GP
authors: Yang
authors: Ze-neng
authors: ZN
authors: Cheng
authors: Zhi
authors: Z
authors: Liu
authors: Pei-jiong
authors: PJ
authors: Li
authors: Hong-yi
authors: HY
authors: Tan
authors: Ling-yun
authors: LY
authors: Zhou
authors: Chung-jiang
authors: CJ
authors: Wang
authors: Meng
authors: M
authors: Yang
mesh_terms: D000284:Administration, Oral; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D017311:Amlodipine; D016559:Tacrolimus