Clinical pharmacology of dronedarone: implications for the therapy of atrial fibrillation.
Dronedarone, a recently approved antiarrhythmic agent, is a chemical analog of amiodarone. It has an approximately 15% bioavailability, with plasma concentrations markedly increasing after a high-fat meal; it is recommended to be taken with food. The primary metabolic clearance pathway for dronedarone is via the hepatic enzyme system (primarily cytochrome P450 3A4 [CYP3A4]); the half-life of dronedarone is 27 to 31 hours. Strong CYP3A4 inhibitors, such as ketoconazole, are associated with a marked increase in dronedarone maximum concentration and are thus contraindicated; inducers of CYP3A4 will conversely decrease dronedarone exposure. Dronedarone is a substrate for P-glycoprotein (P-gp) and will lead to an increase in concentration of P-gp substrates such as digoxin. Dronedarone will cause a small increase in creatinine concentrations, without a change in glomerular filtration rate (GFR). Gender, renal dysfunction, weight, and age have little effect on the pharmacokinetics of dronedarone, and dose adjustment for these variables is not required.
Dorian
Paul
P
Department of Medicine, University of Toronto and Division of Cardiology, St Michael's Hospital, Toronto, Ontario, Canada. dorianp@smh.toronto.on.ca
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D000077764:Dronedarone; D004347:Drug Interactions; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000889:Anti-Arrhythmia Agents; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000077764:Dronedarone; D000638:Amiodarone