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Veterinary sciences2026; 13(5); 445; doi: 10.3390/vetsci13050445

Pharmacokinetics of Ertugliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor (SGLT2i) in Horses After Enteral Administration.

Abstract: Ertugliflozin is a sodium-glucose co-transporter-2 inhibitor that has demonstrated promise as a treatment for hyperinsulinaemia in horses. Despite the frequent use of ertugliflozin in equine clinical practice, the pharmacokinetics of this drug in horses has not been established. The aim of the present study was to determine the pharmacokinetics of one supratherapeutic dose (0.25 mg/kg) of ertugliflozin in eight horses. Horses were defined as being healthy by physical examination, haematological, blood biochemical and oral sugar test (OST) results. Plasma concentrations of ertugliflozin were quantified using high-performance liquid chromatography-tandem mass spectrometry 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 14, 18, 24, 30, 36, 48, 60, 72, 96, and 120 h after drug administration enterally. Non-compartmental analysis led to determination of key pharmacokinetic variables, including mean ± SD time to maximum concentration (T of 0.91 ± 0.13 h, maximum measured concentration (C of 267.52 ± 25.37 ng/mL, terminal elimination half-life (T) of 17.65 ± 3.15 h and apparent oral clearance (CL/F) of 106.95 ± 27.53 mL/h/kg. No clinical signs of adverse effects or blood biochemical abnormalities occurred after drug administration. The results of this study suggest that a single supratherapeutic dose of ertugliflozin in healthy horses is safe. The pharmacokinetics of enterally administered ertugliflozin in horses are similar to pharmacokinetics of the drug in humans and the long T makes ertugliflozin suitable for once daily dosing in horses. It is proposed that a starting dose for ertugliflozin in horses be in the range 0.05-0.1 mg/kg. Further pharmacokinetic studies are required to optimise the dose regimen for treating horses with hyperinsulinaemia.
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Publication Date: 2026-05-01 PubMed ID: 42188915PubMed Central: PMC13211585DOI: 10.3390/vetsci13050445Google Scholar: Lookup
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  • Journal Article

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.

Research Overview

  • This study investigated how the drug ertugliflozin, used to treat high insulin levels, behaves in the bodies of healthy horses after oral administration.
  • The goal was to understand key pharmacokinetic properties to inform safe and effective dosing in equine medicine.

Background and Purpose

  • Ertugliflozin is a sodium-glucose co-transporter-2 inhibitor (SGLT2i), a drug class that reduces blood glucose by promoting glucose excretion via urine.
  • It has shown promise in treating hyperinsulinaemia—a condition of excess insulin—in horses, which can lead to serious metabolic problems.
  • Though used in practice, prior to this study, the pharmacokinetics (PK) of ertugliflozin in horses had not been characterized, meaning optimal dosing and safety profiles were unclear.
  • The research aimed to fill this gap by administering a supratherapeutic dose (higher than the expected therapeutic dose) and measuring how the drug was absorbed, distributed, metabolized, and eliminated.

Methods

  • Eight healthy horses were selected based on physical exams, blood tests, and oral sugar tests to confirm normal health status and metabolic function.
  • Each horse received a single supratherapeutic oral dose of ertugliflozin at 0.25 mg/kg body weight.
  • Blood plasma samples were collected at multiple time points post-administration ranging from immediately before dosing up to 120 hours (5 days) after dosing. Specific time points included very early (0.25, 0.5, 0.75, 1 hour) to later stages (24, 48, 72, 96, 120 hours) to track complete pharmacokinetic profile.
  • Concentrations of ertugliflozin in plasma were measured using sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), a precise technique for drug quantification.
  • Non-compartmental analysis (a standard PK analysis method not assuming a specific compartmental model) was used to calculate key pharmacokinetic parameters.

Key Pharmacokinetic Findings

  • Time to Maximum Concentration (Tmax): On average, 0.91 ± 0.13 hours—indicating rapid absorption after oral dosing.
  • Maximum Plasma Concentration (Cmax): Averaged 267.52 ± 25.37 ng/mL at peak concentration.
  • Terminal Elimination Half-Life (T1/2): Approximately 17.65 ± 3.15 hours, showing the drug remains in the system for a relatively long time, supporting once-daily dosing.
  • Apparent Oral Clearance (CL/F): About 106.95 ± 27.53 mL/h/kg, indicating the rate at which the drug is eliminated relative to the oral dose administered.

Safety and Tolerability

  • No clinical signs of adverse effects were observed in the horses throughout the study.
  • Blood biochemical parameters remained within normal ranges post-administration, suggesting no acute toxicity or organ dysfunction.
  • Thus, a single supratherapeutic dose of ertugliflozin appears safe in healthy horses based on this study.

Comparisons and Implications for Clinical Use

  • Pharmacokinetics in horses were noted to be similar to those reported in humans, indicating potential for cross-species dosing insights.
  • The long elimination half-life supports once-daily dosing, which is practical for veterinary use.
  • Based on the data, the authors propose an initial dosing range of 0.05-0.1 mg/kg for therapeutic use in horses, which is lower than the supratherapeutic dose tested.
  • Further studies are recommended to refine the pharmacokinetic profile at therapeutic doses and to optimize the dose regimen specifically for horses with hyperinsulinaemia.

Conclusions

  • This study provides foundational pharmacokinetic data on ertugliflozin in horses, showing rapid absorption, a long half-life, and good safety at a high dose.
  • The results support ertugliflozin’s potential as a convenient once-daily oral therapy for managing hyperinsulinaemia in horses.
  • Further research is needed to confirm effective dosing strategies and to characterize the drug’s effects in diseased horses rather than only healthy individuals.

Cite This Article

APA
Kirkwood NC, Hughes KJ, Lovett AL, Doran GS, Rendle DI, Edwards SH. (2026). Pharmacokinetics of Ertugliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor (SGLT2i) in Horses After Enteral Administration. Vet Sci, 13(5), 445. https://doi.org/10.3390/vetsci13050445

Publication

Veterinary sciences
ISSN: 2306-7381
NlmUniqueID: 101680127
Country: Switzerland
Language: English
Volume: 13
Issue: 5
PII: 445

Researcher Affiliations

Kirkwood, Naomi C
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Hughes, Kristopher J
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Lovett, Amy L
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Doran, Gregory S
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
  • Gulbali Institute, Charles Sturt University, Albert Pugsley Place, Wagga Wagga, NSW 2678, Australia.
Rendle, David I
  • EMT Consulting, Tiverton EX16 9JU, UK.
Edwards, Scott H
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
  • Gulbali Institute, Charles Sturt University, Albert Pugsley Place, Wagga Wagga, NSW 2678, Australia.

Grant Funding

  • NA / BOVA

Conflict of Interest Statement

Authors D.I.R. works as a consultant to BOVA who funded the research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

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