Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics

Clin Pharmacol Ther. 2007 May;81(5):679-84. doi: 10.1038/sj.clpt.6100098. Epub 2007 Feb 14.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amiodarone / pharmacology*
  • Anti-Arrhythmia Agents / pharmacology*
  • Area Under Curve
  • Biotransformation
  • Cross-Over Studies
  • Drug Interactions
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Organic Anion Transporters / biosynthesis
  • Organic Anion Transporters / genetics
  • Polymorphism, Genetic / genetics
  • Pravastatin / pharmacokinetics*
  • Prospective Studies
  • Simvastatin / pharmacokinetics*
  • Tissue Distribution

Substances

  • Anti-Arrhythmia Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Simvastatin
  • Pravastatin
  • Amiodarone