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Home / Equine Research Bank / J Vet Intern Med / Pharmacokinetics and tolerability of multiple-day oral dosin...
Journal of veterinary internal medicine2023; doi: 10.1111/jvim.16797

Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses.

Abstract: Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Objective: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Methods: Six healthy Standardbred mares. Methods: Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. Results: Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0-12 ) of 12 594 h × ng/mL (8567-19 488 h × ng/mL) and terminal half-life (T1/2 ) of 11.3 hours (7.5-15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. Conclusions: Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
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Publication Date: 2023-07-19 PubMed ID: 37469186DOI: 10.1111/jvim.16797Google 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.

The research article aims to evaluate the pharmacokinetic profile and tolerability of an immunosuppressive drug, Mycophenolate mofetil (MMF), in healthy horses over a seven-day period.

Objective and Methods of the Research

  • The primary objective of this study was to examine the pharmacokinetics (PK) and tolerance of multiple-day oral doses of the drug Mycophenolate mofetil (MMF) in horses.
  • The subjects were six healthy Standardbred mares. These horses were given MMF orally twice daily at dosages of 10 mg/kg over a period of seven days.
  • The researchers collected sampling data every 12 hours on the first day and the seventh day. Additionally, every 24 hours, samples were taken just before morning drug administration.
  • To determine the PK parameters, noncompartmental PK analyses were conducted. After that, the average values and coefficients of variations were calculated.
  • Tolerance to MMF was evaluated through a complete blood count (CBC), serum biochemical profile, physical examination, and fecal scoring.

Findings of the Research

  • After seven days of treatment, the measurements for Mycophenolic acid (MPA) area under the curve (AUC0-12) was found to be 12 594 h × ng/mL, ranging between 8567-19 488 h × ng/mL, and the terminal half-life was 11.3 hours, ranging between 7.5-15.9 hours. This showed minimal metabolite accumulation in all the horses.
  • The researchers found that two horses had salmonella in their feces by the seventh day of treatment.
  • Furthermore, after a week’s treatment with MMF, all the horses exhibited signs of myelosuppression, hyperbilirubinemia, decreased appetite, reduced gastrointestinal motility, and decreased fecal output.

Conclusions of the Research

  • MMF at a dosage of 10 mg/kg given twice daily led to hematologic and clinical toxicity within just one week of administration.
  • Therefore, a reduction in the dosage or frequency of MMF, or both, is necessary to prevent conditions such as colic.
  • The authors further recommend that the monitoring of this drug should include frequent complete blood counts, serum biochemical profiles, and stringent biosecurity protocols.

Cite This Article

APA
Bello K, Lorch G, Kim K, Toribio RE, Yan L, Xie Z, Hill K, Phelps M. (2023). Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses. J Vet Intern Med. https://doi.org/10.1111/jvim.16797

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English

Researcher Affiliations

Bello, Kaitlyn
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Lorch, Gwendolen
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Kim, Kyeongmin
  • Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Toribio, Ramiro E
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Yan, Liwei
  • Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Xie, Zhiliang
  • Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Hill, Kasey
  • Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Phelps, Mitch
  • Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.

Grant Funding

  • Grayson-Jockey Club Research Foundation

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Citations

This article has been cited 1 times.
  1. Lefrançois J, Sauvé F. Overview of the diagnosis and treatment of autoimmune skin disorders in horses. Can Vet J 2024 Sep;65(9):964-969.
    pubmed: 39219600
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