Pharmacokinetics of pioglitazone after multiple oral dose administration in horses

Authors

  • J. M. G. WEARN,

    1. Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
    Search for more papers by this author
  • M. V. CRISMAN,

    1. Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
    Search for more papers by this author
  • J. L. DAVIS,

    1. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
    Search for more papers by this author
  • R. J. GEOR,

    1. Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
    Search for more papers by this author
    • 1

      Present address: Department of Large Animal Clinical Sciences, D202 Veterinary Medical Center, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.

  • D. R. HODGSON,

    1. Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
    Search for more papers by this author
  • J. K. SUAGEE,

    1. Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
    Search for more papers by this author
  • M. ASHRAF-KHORASSANI,

    1. Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
    Search for more papers by this author
  • L. J. McCUTCHEON

    1. Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Leesburg, VA, USA
    Search for more papers by this author
    • 2

      Present address: Department of Pathobiology and Diagnostic Investigation, F 130G Veterinary Medical Center, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.


M. V. Crisman, Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. Tel: (540) 231 4621; fax : (540) 231 1676; E-mail: farmuse@vt.edu

Abstract

Wearn, J.M.G., Crisman, M.V., Davis, J.L., Geor, R.J., Hodgson, D.R., Suagee, J.K., Ashraf-Khorassani, M., McCutcheon, L.J. Pharmacokinetics of pioglitazone after multiple oral dose administration in horses. J. vet. Pharmacol. Therap.

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.

Ancillary