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Interaction between Amlodipine and Simvastatin in Patients with Hypercholesterolemia and Hypertension

2005; Springer Nature; Volume: 28; Issue: 3 Linguagem: Inglês

10.1291/hypres.28.223

1348-4214

Shinichiro Nishio, Hiroshi Watanabe, Kazuhiro Kosuge, Shinya Uchida, Hideharu Hayashi, Kyoichi Ohashi,

Computational Drug Discovery Methods

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are often prescribed in association with antihypertensive agents, including calcium antagonists. Simvastatin is an HMG-CoA reductase inhibitor that is metabolized by the cytochrome P450 (CYP) 3A4. The calcium antagonist amlodipine is also metabolized by CYP3A4. The purpose of this study was to investigate drug interactions between amlodipine and simvastatin. Eight patients with hypercholesterolemia and hypertension were enrolled. They were given 4 weeks of oral simvastatin (5 mg/day), followed by 4 weeks of oral amlodipine (5 mg/day) co-administered with simvastatin (5 mg/day). Combined treatment with simvastatin and amlodipine increased the peak concentration (Cmax) of HMG-CoA reductase inhibitors from 9.6 ±3.7 ng/ml to 13.7±4.7 ng/ml (p<0.05) and the area under the concentration-time curve (AUC) from 34.3±16.5 ng h/ml to 43.9±16.6 ng h/ml (p<0.05) without affecting the cholesterol-lowering effect of simvastatin. This study is the first to determine prospectively the pharmacokinetic and pharmacodynamic interaction between amlodipine and simvastatin.