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Objective—To determine pharmacokinetics and oral bioavailability of metformin in healthy horses.

Animals—4 adult horses.

Procedures—6 g of metformin was administered 3 times IV and PO (fed and unfed) to each horse, by use of a crossover design, with a 1-week washout period between treatments. Plasma metformin concentration was determined via high-pressure liquid chromatography.

Results—Mean ± SD distribution half-life of metformin following IV administration was 24.9 ± 0.4 minutes with a volume of distribution of 0.3 ± 0.1 L/kg. Mean area under the curve was 20.9 ± 2.0 h·μg/mL for IV administration; PO administration resulted in area under the curves of 1.6 ± 0.4 h·μg/mL in unfed horses and 0.8 ± 0.2 h·μg/mL in fed horses. Bioavailability was determined to be approximately 7.1 ± 1.5% in unfed horses and 3.9 ± 1.0% in fed horses. The maximal concentration following PO administration in unfed horses was 0.4 ± 0.1 μg/mL with a time at maximal concentration of 0.9 ± 0.1 hours. In fed horses, maximal concentration was reduced to 0.3 ± 0.04 μg/mL with a time at maximal concentration at 1.3 ± 0.3 hours.

Conclusions and Clinical Relevance—The low bioavailability of metformin may explain the reported lack of clinical success in improving insulin sensitivity with metformin treatment in horses. Dosages and dose intervals previously used may have been insufficient to achieve plasma concentrations of drug comparable to the therapeutic range achieved in humans. Therefore, a larger and more frequently administered dose may be required to fully evaluate efficacy of metformin in horses.

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in American Journal of Veterinary Research