title: Interaction between amlodipine and simvastatin in patients with hypercholesterolemia and hypertension.
abstract: 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 (C(max)) 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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. shinn@hama-med.ac.jp
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nishio
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kosuge
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchida
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000284:Administration, Oral; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017311:Amlodipine; D019821:Simvastatin