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Xenobiotica
the fate of foreign compounds in biological systems
Volume 49, 2019 - Issue 6
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Animal Pharmacokinetics and Metabolism

Dose proportionality and pharmacokinetics of dronedarone following intravenous and oral administration to rat

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Pages 734-739 | Received 29 May 2018, Accepted 30 Jun 2018, Published online: 12 Sep 2018
 

Abstract

  1. The aim of this study was to investigate the pharmacokinetic properties of dronedarone by using noncompartmental analysis and modeling approaches after intravenous and oral administration of dronedarone to rats.

  2. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups, and dronedarone was administered intravenously (1 mg/kg) and orally (5, 10 and 40 mg/kg) based on a parallel design. Blood samples were collected before and 0.083 (intravenous administration only), 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h after drug administration. The plasma concentration of dronedarone was determined by using LC-MS/MS.

  3. The oral bioavailability of dronedarone was evaluated as approximately 16% in rats, similar to that in humans. The assessment of dose proportionality by using the power model showed that AUCinf increased in a dose-proportional manner, whereas AUC24h and Cmax exhibited a lack of dose proportionality over the dose range between 5 and 40 mg/kg. The two-compartment model, with first-order absorption and elimination rate constants, was sufficient to explain the pharmacokinetics of dronedarone with biexponential decay.

  4. These findings will help to understand the pharmacology of dronedarone to develop the new formulation and therapeutics optimization linked to pharmacokinetic/pharmacodynamic study.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

This research was supported by Kyungsung University Research Grants in 2017.

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