Pharmacokinetics and bioavailability of metformin in horses.
Abstract: To determine pharmacokinetics and oral bioavailability of metformin in healthy horses. Methods: 4 adult horses. Methods: 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.microg/mL for IV administration; PO administration resulted in area under the curves of 1.6 +/- 0.4 h.microg/mL in unfed horses and 0.8 +/- 0.2 h.microg/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 microg/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 microg/mL with a time at maximal concentration at 1.3 +/- 0.3 hours. Conclusions: 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.
Publication Date: 2009-05-02 PubMed ID: 19405907DOI: 10.2460/ajvr.70.5.665Google Scholar: Lookup
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- Journal Article
Summary
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This research paper discusses a study on the absorption and distribution (pharmacokinetics) and effectiveness (bioavailability) of a dose of metformin administered to horses, both orally and intravenously.
Study Design and Methods
- The research involved four adult horses, each receiving metformin three times via two methods: orally (with and without food) and intravenously (IV).
- The testing period for each administration was separated by a “washout period” of a week to ensure no residual traces impacted subsequent tests.
- The concentration of metformin in the bloodstream was gauged using high-pressure liquid chromatography.
Results of the Study
- When the drug was administered intravenously, the average half-life (the time taken for the drug concentration to halve) was about 24.9 minutes, and the volume of distribution (the theoretical volume that the drug would have to distribute, in order to provide the same concentration as it is in the blood) was 0.3 litres per kilogram.
- The ‘area under the curve’ (AUC), a measure reflecting the body’s exposure to the drug, was 20.9 per hour for intravenous administration. But for oral administration, the AUC was far lower; 1.6 in unfed horses and 0.8 in fed horses.
- Bioavailability (the proportion of the drug that enters circulation to have an active effect) was also low – approximately 7.1% in unfed horses and 3.9% in fed horses. This suggests that a minuscule portion of the drug was being effectively absorbed when given orally.
Conclusions and Implications
- The study concluded that the low bioavailability of metformin could be why it has not proven effective at improving insulin sensitivity in horses – the level reached in their bloodstream was potentially too low to have an effect.
- As such, the dosages and frequency of administering metformin used in previous attempts to improve insulin sensitivity in horses may have been insufficient.
- Therefore, researchers suggest a larger, more frequently administered dose could be needed to evaluate truly the efficacy of metformin therapy in horses.
Cite This Article
APA
Hustace JL, Firshman AM, Mata JE.
(2009).
Pharmacokinetics and bioavailability of metformin in horses.
Am J Vet Res, 70(5), 665-668.
https://doi.org/10.2460/ajvr.70.5.665 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
MeSH Terms
- Administration, Oral
- Animals
- Biological Availability
- Cross-Over Studies
- Female
- Horses
- Hypoglycemic Agents / administration & dosage
- Hypoglycemic Agents / adverse effects
- Hypoglycemic Agents / chemistry
- Hypoglycemic Agents / pharmacokinetics
- Infusions, Intravenous / veterinary
- Male
- Metformin / administration & dosage
- Metformin / adverse effects
- Metformin / chemistry
- Metformin / pharmacokinetics
- Time Factors
Citations
This article has been cited 14 times.- de Tonnerre DJ, Medina Torres CE, Stefanovski D, Robinson MA, Kemp KL, Bertin FR, van Eps AW. Effect of sirolimus on insulin dynamics in horses.. J Vet Intern Med 2023 Mar;37(2):703-712.
- Bouriche S, Alonso-García A, Cárceles-Rodríguez CM, Rezgui F, Fernández-Varón E. An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits.. BMC Vet Res 2021 Sep 25;17(1):315.
- Jeong YS, Jusko WJ. Meta-Assessment of Metformin Absorption and Disposition Pharmacokinetics in Nine Species.. Pharmaceuticals (Basel) 2021 Jun 7;14(6).
- Ericsson AC, Johnson PJ, Gieche LM, Zobrist C, Bucy K, Townsend KS, Martin LM, LaCarrubba AM. The Influence of Diet Change and Oral Metformin on Blood Glucose Regulation and the Fecal Microbiota of Healthy Horses.. Animals (Basel) 2021 Apr 1;11(4).
- Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, Murbartián J, Torres-López JE, Granados-Soto V. Metformin: A Prospective Alternative for the Treatment of Chronic Pain.. Front Pharmacol 2020;11:558474.
- Marycz K, Szłapka-Kosarzewska J, Geburek F, Kornicka-Garbowska K. Systemic Administration of Rejuvenated Adipose-Derived Mesenchymal Stem Cells Improves Liver Metabolism in Equine Metabolic Syndrome (EMS)- New Approach in Veterinary Regenerative Medicine.. Stem Cell Rev Rep 2019 Dec;15(6):842-850.
- Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome.. J Vet Intern Med 2019 Mar;33(2):335-349.
- de Laat MA, Kheder MH, Pollitt CC, Sillence MN. Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation.. PLoS One 2018;13(6):e0200070.
- Díez R, García JJ, Diez MJ, Sierra M, Sahagun AM, Fernández N. Influence of Plantago ovata husk (dietary fiber) on the bioavailability and other pharmacokinetic parameters of metformin in diabetic rabbits.. BMC Complement Altern Med 2017 Jun 7;17(1):298.
- Morgan R, Keen J, McGowan C. Equine metabolic syndrome.. Vet Rec 2015 Aug 15;177(7):173-9.
- Lacombe VA. Expression and regulation of facilitative glucose transporters in equine insulin-sensitive tissue: from physiology to pathology.. ISRN Vet Sci 2014;2014:409547.
- Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK. Effect of dietary nonstructural carbohydrate content on activation of 5'-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies.. J Vet Intern Med 2014 Jul-Aug;28(4):1280-8.
- Johnson PJ, Wiedmeyer CE, LaCarrubba A, Ganjam VK, Messer NT 4th. Diabetes, insulin resistance, and metabolic syndrome in horses.. J Diabetes Sci Technol 2012 May 1;6(3):534-40.
- Giri JK, Magdesian KG, Gaffney PM. Insulin-dependent diabetes mellitus associated with presumed autoimmune polyendocrine syndrome in a mare.. Can Vet J 2011 May;52(5):506-12.
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