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)0-24 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.
Becquemont
L
L
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
Neuvonen
M
M
Verstuyft
C
C
Jaillon
P
P
Letierce
A
A
Neuvonen
P J
PJ
Funck-Brentano
C
C
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
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