Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics

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 ( C-max), and t(1/2) 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 AUC(0-24) 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.