title: Clinical pharmacology of dronedarone: implications for the therapy of atrial fibrillation.
abstract: 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.
authors.affiliation: Department of Medicine, University of Toronto and Division of Cardiology, St Michael's Hospital, Toronto, Ontario, Canada. dorianp@smh.toronto.on.ca
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
mesh_terms: 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
chemical_list: 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