A pharmacokinetic and pharmacodynamic study of pioglitazone in a model of induced insulin resistance in normal horses
Equine Metabolic Syndrome (EMS) is a unique condition of horses characterized by adiposity, insulin resistance, and an increased risk of laminitis. Reducing insulin resistance may decrease the incidence of laminitis in horses with EMS. Pioglitazone, a thiazolidinedione class of anti-diabetic drug...
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Virginia Tech
2014
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Online Access: | http://hdl.handle.net/10919/33921 http://scholar.lib.vt.edu/theses/available/etd-07072010-090728/ |
Summary: | Equine Metabolic Syndrome (EMS) is a unique condition of horses characterized by
adiposity, insulin resistance, and an increased risk of laminitis. Reducing insulin
resistance may decrease the incidence of laminitis in horses with EMS. Pioglitazone, a
thiazolidinedione class of anti-diabetic drug, has proven efficacy in humans with type 2
diabetes, a syndrome of insulin resistance sharing some similarities with EMS. The
ability of pioglitazone to influence insulin sensitivity in an endotoxin-infusion model of
induced insulin resistance was investigated. Our hypothesis was that piogltiazone would
preserve insulin sensitivity in a model of induced insulin resistance. The specific aims
were to investigate the pharmacokinetics and pharmacodynamics of pioglitazone in an
endotoxin infusion model of insulin resistance.<p>
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.<p>
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. === Master of Science |
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