Pharmacokinetics of pioglitazone after multiple oral dose administration in horses

Wearn, J.M.G., Crisman, M.V., Davis, J.L., Geor, R.J., Hodgson, D.R., Suagee, J.K., Ashraf-Khorassani, M., and McCutcheon, L.J. (2011) Pharmacokinetics of pioglitazone after multiple oral dose administration in horses. Journal of Veterinary Pharmacology and Therapeutics, 34 (3). pp. 252-258.

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Abstract

Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter the drug was administered to six horses. Samples were analyzed by liquid chromatography with tandem mass spectrometry, and pharmacokinetic parameters were calculated using noncompartmental modeling. The maximum plasma concentration was 509.1 ± 413.5 ng/mL achieved at 1.88 ± 1.39 h following oral administration of the first dose, and 448.1 ± 303.5 ng/mL achieved at 2.83 ± 1.81 h (mean ± SD) following the eleventh dose. Apparent elimination half-life was 9.94 ± 4.57 and 9.63 ± 5.33 h after the first and eleventh dose, respectively. This study showed that in healthy horses, pioglitazone administered at a daily oral dose of 1 mg/kg results in plasma concentrations and total drug exposure approximating, but slightly below, those considered therapeutic in humans.

Item ID: 40141
Item Type: Article (Research - C1)
ISSN: 1365-2885
Funders: Centre for Equine Research in Virginia
Date Deposited: 28 Oct 2015 03:26
FoR Codes: 07 AGRICULTURAL AND VETERINARY SCIENCES > 0707 Veterinary Sciences > 070710 Veterinary Pharmacology @ 100%
SEO Codes: 83 ANIMAL PRODUCTION AND ANIMAL PRIMARY PRODUCTS > 8303 Livestock Raising > 830306 Horses @ 100%
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