Amiodarone Interacts with Simvastatin but not with Pravastatin Disposition Kinetics.
Becquemont, L 1,2,3,4; Neuvonen, M 5; Verstuyft, C 1,3,4; Jaillon, P 6,7; Letierce, A 2; Neuvonen, P J 5; Funck-Brentano, C 6,7,8,9
[Article]
Clinical Pharmacology & Therapeutics.
81(5):679-684, May 2007.
(Format: HTML, PDF)
The aim of this study was to determine the influence of amiodarone on the pharmacokinetics of simvastatin and pravastatin in humans. This was a prospective, crossover, randomized, open-label study performed in 12 healthy volunteers comparing the pharmacokinetics of a single oral dose of simvastatin (40 mg) or pravastatin (40 mg) taken alone and after 3 days of amiodarone (400 mg/day). Amiodarone increased simvastatin acid AUC (area under the plasma concentration-time curve)0-24h, peak plasma concentration (Cmax), and t1/2 by 73% (P = 0.02), 100% (P = 0.02), and 48% (P = 0.06), respectively, whereas it did not significantly alter pravastatin pharmacokinetics. Point estimates and 90% confidence intervals for simvastatin acid, simvastatin lactone, and pravastatin AUC0-24h were 154% (109-216%), 155% (109-227%), and 86% (63-118%), respectively. If amiodarone and a statin have to be simultaneously prescribed, pravastatin should be preferred to simvastatin in order to avoid a drug interaction.
(C) Mosby-Year Book Inc. 2007. All Rights Reserved.