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Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics
L Becquemont1, M Neuvonen, C Verstuyft
1Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Génétique Moléculaire et Pharmacogénétique, and Départment de Pharmacologie, Université Paris-Sud (XI), Le Kremlin Bicetre, France. laurent.becquemont@bct.aphp.fr
Abstract:
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)0-24 h, 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 AUC0-24 h 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.
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