title: Pharmacokinetics of pioglitazone after multiple oral dose administration in horses.
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.
authors.affiliation: Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: J M G
authors.initials: JM
authors.lastname: Wearn
authors.forename: M V
authors.initials: MV
authors.lastname: Crisman
authors.forename: J L
authors.initials: JL
authors.lastname: Davis
authors.forename: R J
authors.initials: RJ
authors.lastname: Geor
authors.forename: D R
authors.initials: DR
authors.lastname: Hodgson
authors.forename: J K
authors.initials: JK
authors.lastname: Suagee
authors.forename: M
authors.initials: M
authors.lastname: Ashraf-Khorassani
authors.forename: L J
authors.initials: LJ
authors.lastname: McCutcheon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077205:Pioglitazone; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000662:veterinary; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; D013607:Tablets; D045162:Thiazolidinediones; D000077205:Pioglitazone