Effect of dronedarone on the pharmacokinetics of carvedilol following oral administration to rats.
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Kim MS, Baek IH
Effect of dronedarone on the pharmacokinetics of carvedilol following oral administration to rats.
Eur J Pharm Sci. 2018 Jan 1;111:13-19. doi: 10.1016/j.ejps.2017.09.029. Epub 2017 Sep 20.
- PubMed ID
- 28942006 [ View in PubMed]
- Abstract
Dronedarone is a CYP2D6 inhibitor; therefore, it is prudent to exercise caution when concurrently administering CYP2D6-metabolized beta-blockers because of a lack of published data on potential drug interactions. The aim of this study was to investigate the effect of dronedarone on the pharmacokinetics of orally administered carvedilol in rats. Twenty male Sprague-Dawley rats were randomly divided into two groups and 10mg/kg carvedilol was administered to the rat with or without dronedarone pretreatment in a parallel design. Blood samples were collected before and after 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24h of drug administration. The plasma concentration of carvedilol was determined using LC-MS/MS. The systemic exposure to carvedilol was significantly increased and elimination of carvedilol was significantly decreased in the dronedarone-pretreated rats than in the vehicle-pretreated rats. The one-compartment model with first-order absorption and elimination was sufficient to explain the pharmacokinetic characters after single oral administration of carvedilol to both vehicle-pretreated and dronedarone-pretreated rats. This study suggests that dronedarone inhibits CYP2D6-mediated carvedilol metabolism, and dose adjustment is needed in carvedilol and dronedarone combination therapy. Further studies are needed to clarify the effect of dronedarone on carvedilol and CYP2D6 substrates in clinical use.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Dronedarone Cytochrome P450 2D6 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcetaminophenDronedarone The metabolism of Acetaminophen can be decreased when combined with Dronedarone. AlmotriptanDronedarone The metabolism of Almotriptan can be decreased when combined with Dronedarone. AlogliptinDronedarone The metabolism of Alogliptin can be decreased when combined with Dronedarone. AminophenazoneDronedarone The metabolism of Aminophenazone can be decreased when combined with Dronedarone. AmphetamineDronedarone The metabolism of Amphetamine can be decreased when combined with Dronedarone.