A pharmacokinetic and pharmacodynamic study of pioglitazone in a model of induced insulin resistance in normal horses
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16 normal adult horses were enrolled. Pioglitazone was administered to 8 horses (1 mg/kg, PO, q24h) for 14 days, and 8 horses served as their controls. Liquid chromatography with tandem mass spectroscopy was used to quantitate plasma concentration of pioglitazone. A frequently sampled intravenous glucose tolerance test with minimum model analysis was used to compare indices of glucose and insulin dynamics prior to, and following, endotoxin infusion in horses treated with pioglitazone and their controls. Parameters of clinical examination and lipid metabolism were compared prior to, and following, endotoxin administration.
Pioglitazone administered orally at 1 mg/kg q 24 h resulted in plasma concentrations lower, and more variable, compared to those considered therapeutic in humans. No significant effect of drug treatment was detected on clinical parameters or indices of insulin dynamics or lipid homeostasis following endotoxin challenge.
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