title: Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics.
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.
authors.affiliation: Assistance 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
authors.forename: L
authors.initials: L
authors.lastname: Becquemont
authors.forename: M
authors.initials: M
authors.lastname: Neuvonen
authors.forename: C
authors.initials: C
authors.lastname: Verstuyft
authors.forename: P
authors.initials: P
authors.lastname: Jaillon
authors.forename: A
authors.initials: A
authors.lastname: Letierce
authors.forename: P J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: C
authors.initials: C
authors.lastname: Funck-Brentano
mesh_terms: D000328:Adult; D000638:Amiodarone / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001711:Biotransformation; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D017035:Pravastatin / Q000493:pharmacokinetics*; D011446:Prospective Studies; D019821:Simvastatin / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000889:Anti-Arrhythmia Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D019821:Simvastatin; D017035:Pravastatin; D000638:Amiodarone