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Home / Equine Research Bank / J Vet Pharmacol Ther / Pharmacokinetics and Alterations in Glucose and Insulin Leve...
Journal of veterinary pharmacology and therapeutics2024; 48 Suppl 1(Suppl 1); 41-49; doi: 10.1111/jvp.13476

Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses.

Abstract: Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC-MS/MS). A non-compartmental analysis revealed key pharmacokinetic parameters, including a median Tmax of 7 h, a Cmax of 2350 ng/mL, and a t1/2Z of 28.5 h. CFZ treatment reduced glucose (AUCGLU, p = 0.001) and insulin (AUCINS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.
© 2024 The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
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Publication Date: 2024-08-07 PubMed ID: 39113254PubMed Central: PMC11736998DOI: 10.1111/jvp.13476Google Scholar: Lookup
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  • Journal Article
  • Clinical Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The researchers studied how a single oral dose of the drug Canagliflozin affects the insulin and glucose levels in healthy Icelandic horses. They also investigated the distribution, breakdown and elimination of the drug in the horses’ bodies.

Understanding Canagliflozin

  • The medicine being studied is Canagliflozin (CFZ), a sodium-glucose cotransporter-2 inhibitor which is used to control insulin levels. It has shown promise for treating insulin dysregulation in horses.

The Study Design

  • The study observed the effects and processed associated with CFZ in the bodies of eight healthy Icelandic horses – these horses were given a single oral dose of 1.8 mg/kg.
  • Researchers tested the horses’ plasma samples at various intervals ranging from immediately after administration to 48 hours post-administration.
  • They used a method known as UHPLC-MS/MS (Ultra-High Performance Liquid Chromatography coupled to Tandem Quadrupole Mass Spectrometry) to measure the amount of CFZ in the plasma samples.
  • This allowed them to track how the drug moved through, and interacted with, the horses’ bodies over time.

Key Findings

  • The key pharmacokinetic parameters, which include properties such as the time taken for peak concentration (median T – 7 hours), peak concentration (C – 2350 ng/mL), and the time taken for the drug concentration to decrease by half (t – 28.5 hours), were calculated.
  • The researchers found that a single dose of CFZ rapidly reduced both glucose and insulin responses in the horses when a graded glucose infusion was administered 5 hours after the treatment.
  • The rapid onset of effects indicates that CFZ could be an effective treatment in controlling insulin and glucose levels in horses.

Safety of the Treatment

  • No obvious adverse effects were reported in the horses after the administration of CFZ, which suggests that the drug is safe for use, at least in the short term. However, it’s important to note that more studies may be needed to confirm long-term safety and effectiveness.

Cite This Article

APA
Michanek P, Bröjer J, Lilliehöök I, Fjordbakk CT, Löwgren M, Hedeland M, Bergquist J, Ekstrand C. (2024). Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses. J Vet Pharmacol Ther, 48 Suppl 1(Suppl 1), 41-49. https://doi.org/10.1111/jvp.13476

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 48 Suppl 1
Issue: Suppl 1
Pages: 41-49

Researcher Affiliations

Michanek, Peter
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Bröjer, Johan
  • Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Lilliehöök, Inger
  • Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Fjordbakk, Cathrine T
  • Department of Companion Animal Clinical Sciences, Norwegian University of Life Sciences, Oslo, Norway.
Löwgren, Minerva
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Hedeland, Mikael
  • Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
Bergquist, Jonas
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
  • Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
Ekstrand, Carl
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.

MeSH Terms

  • Animals
  • Horses / blood
  • Horses / metabolism
  • Canagliflozin / pharmacokinetics
  • Canagliflozin / administration & dosage
  • Canagliflozin / blood
  • Insulin / blood
  • Blood Glucose / drug effects
  • Blood Glucose / analysis
  • Male
  • Female
  • Area Under Curve
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacokinetics
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage
  • Half-Life
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / administration & dosage

Grant Funding

  • The Swedish-Norwegian Foundation for Equine Research/Stiftelsen Hästforskning

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 38 references
  1. Asplin KE, Sillence MN, Pollitt CC, McGowan CM. Induction of Laminitis by Prolonged Hyperinsulinaemia in Clinically Normal Ponies. Veterinary Journal 174, no. 3: 530–535.
    doi: 10.1016/j.tvjl.2007.07.003pubmed: 17719811google scholar: lookup
  2. Byrne MM, Sturis J, Polonsky KS. Insulin Secretion and Clearance During Low‐Dose Graded Glucose Infusion. American Journal of Physiology 268, no. 1 Pt 1: E21–E27.
    doi: 10.1152/ajpendo.1995.268.1.E21pubmed: 7840177google scholar: lookup
  3. Carter RA, Geor RJ, Burton Staniar W, Cubitt TA, Harris PA. Apparent Adiposity Assessed by Standardised Scoring Systems and Morphometric Measurements in Horses and Ponies. Veterinary Journal (London, England: 1997) 179, no. 2: 204–210.
    doi: 10.1016/j.tvjl.2008.02.029pubmed: 18440844google scholar: lookup
  4. Chameroy K, Frank N, Elliott S. Effects of Levothyroxine Sodium on Body Condition, Blood Measures of Metabolic Status,and Glucose Dynamics in Horses With Equine Metabolic Syndrome (EMS). Journal of Veterinary Internal Medicine 24, no. 3: 780.
    doi: 10.1111/j.1939-1676.2010.0521.x?download=truegoogle scholar: lookup
  5. Colmer SF, Adams AA, Adam E. The Effect of Pre‐Dosing With Metformin on the Insulin Response to Oral Sugar in Insulin‐Dysregulated Horses. Equine Veterinary Journal 56, no. 2: 318–325.
    doi: 10.1111/evj.13979pubmed: 37545128google scholar: lookup
  6. de Laat MA, McGowan CM, Sillence MN, Pollitt CC. Equine Laminitis: Induced by 48 h Hyperinsulinaemia in Standardbred Horses. Equine Veterinary Journal 42, no. 2: 129–135.
    doi: 10.2746/042516409x475779pubmed: 20156248google scholar: lookup
  7. Devineni D, Murphy J, Wang SS. Absolute Oral Bioavailability and Pharmacokinetics of Canagliflozin: A Microdose Study in Healthy Participants. Clinical Pharmacology in Drug Development 4, no. 4: 295–304.
    doi: 10.1002/cpdd.162pubmed: 27136910google scholar: lookup
  8. Devineni D, Polidori D. Clinical Pharmacokinetic, Pharmacodynamic, and Drug–Drug Interaction Profile of Canagliflozin, A Sodium‐Glucose Co‐transporter 2 Inhibitor. Clinical Pharmacokinetics 54, no. 10: 1027–1041.
    doi: 10.1007/s40262-015-0285-zpubmed: 26041408google scholar: lookup
  9. Dong S-T, Niu H-M, Wu Y. Plasma Pharmacokinetic Determination of Canagliflozin and Its Metabolites in a Type 2 Diabetic Rat Model by UPLC‐MS/MS. Molecules 23, no. 5: 1229.
    doi: 10.3390/molecules23051229pmc: PMC6100046pubmed: 29783787google scholar: lookup
  10. Durham AE, Frank N, Mcgowan CM. ECEIM Consensus Statement On Equine Metabolic Syndrome. Journal of Veterinary Internal Medicine 33, no. 2: 335–349.
    doi: 10.1111/jvim.15423pmc: PMC6430910pubmed: 30724412google scholar: lookup
  11. Durham AE, Rendle DI, Newton JR. The Effect of Metformin on Measurements of Insulin Sensitivity and β Cell Response in 18 Horses and Ponies With Insulin Resistance. Equine Veterinary Journal 40, no. 5: 493–500.
    doi: 10.2746/042516408x273648pubmed: 18482898google scholar: lookup
  12. ElSayed NA, Aleppo G, Aroda VR. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care 46, S140–S157.
    doi: 10.2337/dc23-S009pmc: PMC9810476pubmed: 36507650google scholar: lookup
  13. Frank N, Elliott SB, Boston RC. Effects of Long‐Term Oral Administration of Levothyroxine Sodium on Glucose Dynamics in Healthy Adult Horses. American Journal of Veterinary Research 69, no. 1: 76–81.
    doi: 10.2460/ajvr.69.1.76pubmed: 18167090google scholar: lookup
  14. Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MDS. Efficacy, Safety and Regulatory Status of SGLT2 Inhibitors: Focus on Canagliflozin. Nutrition & Diabetes 4, no. 11: e143.
    doi: 10.1038/nutd.2014.40pmc: PMC4259905pubmed: 25365416google scholar: lookup
  15. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship Between Condition Score, Physical Measurements and Body Fat Percentage in Mares. Equine Veterinary Journal 15, no. 4: 371–372.
    doi: 10.1111/j.2042-3306.1983.tb01826.xpubmed: 6641685google scholar: lookup
  16. Hustace JL, Firshman AM, Mata JE. Pharmacokinetics and Bioavailability of Metformin in Horses. American Journal of Veterinary Research 70, no. 5: 665–668.
    doi: 10.2460/ajvr.70.5.665pubmed: 19405907google scholar: lookup
  17. Kellon EM, Gustafson KM. Use of the SGLT2 Inhibitor Canagliflozin for Control of Refractory Equine Hyperinsulinemia and Laminitis. Open Veterinary Journal 12, no. 4: 511–518.
    doi: 10.5455/OVJ.2022.v12.i4.14pmc: PMC9473365pubmed: 36118716google scholar: lookup
  18. Kellon EM, Gustafson KM. Hypertriglyceridemia in Equines With Refractory Hyperinsulinemia Treated With SGLT2 Inhibitors. Open Veterinary Journal 13, no. 3: 365–375.
    doi: 10.5455/OVJ.2023.v13.i3.14pmc: PMC10072834pubmed: 37026076google scholar: lookup
  19. Lin JD, Wu CZ, Tang WH. Comparison of Second‐Phase Insulin Secretion Derived From Standard and Modified Low‐Dose Graded Glucose Infusion Tests. Canadian Journal of Diabetes 40, no. 6: 529–534.
    doi: 10.1016/j.jcjd.2016.03.007pubmed: 27247269google scholar: lookup
  20. Lindase S, Nostell K, Forslund A, Bergsten P, Brojer J. Short‐Term Effects of Canagliflozin on Glucose and Insulin Responses in Insulin Dysregulated Horses: A Randomized, Placebo‐Controlled, Double‐Blind, Study. Journal of Veterinary Internal Medicine 37, no. 6: 2520–2528.
    doi: 10.1111/jvim.16906pmc: PMC10658518pubmed: 37864426google scholar: lookup
  21. Luthersson N, Mannfalk M, Parkin TDH, Harris P. Laminitis: Risk Factors and Outcome in a Group of Danish Horses. Journal of Equine Veterinary Science 53: 68–73.
    doi: 10.1016/j.jevs.2016.03.006google scholar: lookup
  22. Macon EL, Harris P, Bailey S, Barker VD, Adams A. Postprandial Insulin Responses to Various Feedstuffs Differ in Insulin Dysregulated Horses Compared With Non‐insulin Dysregulated Controls. Equine Veterinary Journal 54, no. 3: 574–583.
    doi: 10.1111/evj.13474pubmed: 34053111google scholar: lookup
  23. Macon EL, Harris P, Bailey S, Caldwell Barker A, Adams A. Identifying Possible Thresholds for Nonstructural Carbohydrates in the Insulin Dysregulated Horse. Equine Veterinary Journal 55, no. 6: 1069–1077.
    doi: 10.1111/evj.13910pubmed: 36537847google scholar: lookup
  24. Meier A, De Laat M, Reiche D, Fitzgerald D, Sillence M. The Efficacy and Safety of Velagliflozin Over 16 Weeks as a Treatment for Insulin Dysregulation in Ponies. BMC Veterinary Research 15, no. 1: 65.
    doi: 10.1186/s12917-019-1811-2pmc: PMC6390376pubmed: 30808423google scholar: lookup
  25. Meier A, Reiche D, De Laat M, Pollitt C, Walsh D, Sillence M. The Sodium‐Glucose Co‐Transporter 2 Inhibitor Velagliflozin Reduces Hyperinsulinemia and Prevents Laminitis in Insulin‐Dysregulated Ponies. PLoS One 13, no. 9: e0203655.
    doi: 10.1371/journal.pone.0203655pmc: PMC6136744pubmed: 30212530google scholar: lookup
  26. Öberg J, Bröjer J, Wattle O, Lilliehöök I. Evaluation of an Equine‐Optimized Enzyme‐Linked Immunosorbent Assay for Serum Insulin Measurement and Stability Study of Equine Serum Insulin. Comparative Clinical Pathology 21, no. 6: 1291–1300.
    doi: 10.1007/s00580-011-1284-6google scholar: lookup
  27. Polidori D, Sha S, Mudaliar S. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion. Diabetes Care 36, no. 8: 2154–2161.
    doi: 10.2337/dc12-2391pmc: PMC3714520pubmed: 23412078google scholar: lookup
  28. nR Core Teamn. 2023. _R: A Language and Environment for Statistical Computing_. R Foundation for Statistical Computing, Vienna, Austria. https://www.R‐project.org/.
  29. Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE. Effects of Metformin Hydrochloride on Blood Glucose and Insulin Responses to Oral Dextrose in Horses. Equine Veterinary Journal 45, no. 6: 751–754.
    doi: 10.1111/evj.12068pubmed: 23600690google scholar: lookup
  30. Sha S, Devineni D, Ghosh A. Canagliflozin, a Novel Inhibitor of Sodium Glucose Co‐Transporter 2, Dose Dependently Reduces Calculated Renal Threshold for Glucose Excretion and Increases Urinary Glucose Excretion in Healthy Subjects. Diabetes, Obesity and Metabolism 13, no. 7: 669–672.
    doi: 10.1111/j.1463-1326.2011.01406.xpubmed: 21457428google scholar: lookup
  31. Sommardahl CS, Frank N, Elliott SB. Effects of Oral Administration of Levothyroxine Sodium on Serum Concentrations of Thyroid Gland Hormones and Responses to Injections of Thyrotropin‐Releasing Hormone in Healthy Adult Mares. American Journal of Veterinary Research 66, no. 6: 1025–1031.
    doi: 10.2460/ajvr.2005.66.1025pubmed: 16008227google scholar: lookup
  32. Stewart-Hunt L, Geor RJ, Mccutcheon LJ. Effects of Short‐Term Training on Insulin Sensitivity and Skeletal Muscle Glucose Metabolism in Standardbred Horses. Equine Veterinary Journal 38, no. S36: 226–232.
    doi: 10.1111/j.2042-3306.2006.tb05544.xpubmed: 17402423google scholar: lookup
  33. Sundra T, Kelty E, Rendle D. Preliminary Observations on the Use of Ertugliflozin in the Management of Hyperinsulinaemia and Laminitis in 51 Horses: A Case Series. Equine Veterinary Education 35, no. 6: 311–320.
    doi: 10.1111/eve.13738google scholar: lookup
  34. Tinworth KD, Edwards S, Harris PA, Sillence MN, Hackett LP, Noble GK. Pharmacokinetics of Metformin After Enteral Administration in Insulin‐Resistant Ponies. American Journal of Veterinary Research 71, no. 10: 1201–1206.
    doi: 10.2460/ajvr.71.10.1201pubmed: 20919907google scholar: lookup
  35. Van Weyenberg S, Hesta M, Buyse J, Janssens GPJ. The Effect of Weight Loss by Energy Restriction on Metabolic Profile and Glucose Tolerance in Ponies. Journal of Animal Physiology and Animal Nutrition 92, no. 5: 538–545.
    doi: 10.1111/j.1439-0396.2007.00744.xpubmed: 19012597google scholar: lookup
  36. Vick MM, Sessions DR, Murphy BA, Kennedy EL, Reedy SE, Fitzgerald BP. Obesity Is Associated With Altered Metabolic and Reproductive Activity in the Mare: Effects of Metformin on Insulin Sensitivity and Reproductive Cyclicity. Reproduction, Fertility and Development 18, no. 6: 609.
    doi: 10.1071/rd06016pubmed: 16930507google scholar: lookup
  37. Vinarov Z, Abdallah M, Agundez JAG. Impact of Gastrointestinal Tract Variability on Oral Drug Absorption and Pharmacokinetics: An UNGAP Review. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences 162: 105812.
    doi: 10.1016/j.ejps.2021.105812pubmed: 33753215google scholar: lookup
  38. Zhou X, Cassidy KC, Hudson L, Mohutsky MA, Sawada GA, Hao J. Enterohepatic Circulation of Glucuronide Metabolites of Drugs in Dog. Pharmacology Research & Perspectives 7, no. 4: e00502.
    doi: 10.1002/prp2.502pmc: PMC6609541pubmed: 31333846google scholar: lookup
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