The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses.
Abstract: Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six-day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p = .038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single-dose administration but may be significant in horses receiving long-term MMF treatment.
© 2024 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
Publication Date: 2024-02-09 PubMed ID: 38334367DOI: 10.1111/jvp.13430Google Scholar: Lookup
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- Journal Article
Summary
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This research studies the changes in absorption rate of the drug mycophenolate mofetil (MMF) in horses given the medicine in a fed and fasted state. The study found that a single dose administration of MMF in a fasted state resulted in higher plasma metabolite concentrations than in a fed state at a certain time point.
Research Purpose and Methodology
- The primary objective of this study was to explore the pharmacokinetics, that is, the body’s process of absorbing, distributing, metabolising, and excreting a drug, of MMF in healthy horses under the conditions of being fed and fasted.
- The drug MMF, which is commonly used in human and veterinary medicine to prevent graft (transplant) rejection and managing autoimmune disorders, was administered at a 10 mg/kg dosage through a nasogastric (NG) tube to six healthy Standardbred mare horses in both states.
- To ensure elimination of the drug before switching states, a six-day washout period was employed between the two administrations.
Study Findings
- There was no statistically significant disparity in the concentrations of mycophenolic acid (MPA), a metabolite of MMF, at any point in time except for 8 hours post administration. During this period, significantly higher MPA levels were observed in the horses when fasted compared to when fed.
- This suggests that the feeding conditions of the horse might influence the pharmacokinetics of MMF, specifically its absorption rate in the digestive system.
- In the fasted state, evidence of enterohepatic recirculation was found, which refers to the process where the drug, after being metabolised in the liver, is excreted into the bile, reabsorbed in the intestine, and returned to the liver. This cycle was not observed in the fed state.
- While this enterohepatic recirculation did not trigger noticeable clinical differences in horses given a single dose, the study suggests it may have significant implications for horses under long-term treatment with MMF.
Implications of the study
- This study contributes to the limited body of research investigating the pharmacokinetics of MMF in horses, and provides crucial information that could assist in optimising dosage strategies.
- Further investigations are needed to understand how variations in feeding states may affect longer term MMF treatment in horses suffering from immune-mediated diseases.
Cite This Article
APA
Bello K, Lorch G, Papich MG, Kim K, Toribio RE, Yan L, Xie Z, Hill K, Phelps MA.
(2024).
The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses.
J Vet Pharmacol Ther.
https://doi.org/10.1111/jvp.13430 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
- Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Grant Funding
- The Grayson-Jockey Club Research Foundation
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