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Effect of atorvastatin on the intravenous and oral pharmacokinetics of verapamil in rats
Author(s) -
Choi DongHyun,
Chang KyongSig,
Hong SoonPyo,
Choi JunShik,
Han HyoKyung
Publication year - 2008
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.582
Subject(s) - verapamil , atorvastatin , pharmacokinetics , bioavailability , pharmacology , oral administration , drug interaction , medicine , cyp3a4 , chemistry , metabolism , cytochrome p450 , calcium
The present study aimed to investigate the effect of atorvastatin on the intravenous and oral pharmacokinetics of verapamil in rats. The pharmacokinetic parameters of verapamil were measured after an oral (9 mg/kg) or intravenous (3 mg/kg) administration of verapamil to rats in the presence and absence of atorvastatin. Compared with the control given verapamil alone, the concurrent use of 1.5 mg/kg of atorvastatin significantly increased the oral exposure of verapamil in rats. The AUC and C max of verapamil increased by 70% and 61%, respectively in the presence of atorvastatin (1.5 mg/kg), while there was no significant change in T max and the terminal plasma half‐life ( T 1/2 ) of verapamil. Accordingly, the presence of atorvastatin significantly ( p <0.05) increased the bioavailability of verapamil in rats. In contrast, atorvastatin had no effect on any pharmacokinetic parameters of verapamil given intravenously, implying that atorvastatin may improve the oral bioavailability of verapamil by reducing the prehepatic extraction of verapamil most likely mediated by P‐gp and/or CYP3A4. In conclusion, coadministration of atorvastatin significantly enhanced the oral exposure of verapamil in rats without a change in the systemic clearance of intravenous verapamil, suggesting a potential drug interaction between verapamil and atorvastatin via the modulation of prehepatic extraction. Copyright © 2007 John Wiley & Sons, Ltd.