Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses.
Authors: Bello Kaitlyn, Lorch Gwendolen, Kim Kyeongmin, Toribio Ramiro E, Yan Liwei, Xie Zhiliang, Hill Kasey, Phelps Mitch
Journal: Journal of veterinary internal medicine
Summary
# Mycophenolate Mofetil in Horses: Pharmacokinetics and Safety Concerns Mycophenolate mofetil (MMF) represents a potentially useful immunosuppressive option for treating immune-mediated diseases in horses, but its safety profile at therapeutic doses remains unclear. Researchers administered MMF at 10 mg/kg orally twice daily for seven days to six healthy Standardbred mares, collecting blood samples intensively on Days 1 and 7, with trough measurements taken before each morning dose, whilst monitoring clinical signs, complete blood counts, serum biochemistry, and faecal output throughout. The drug showed predictable pharmacokinetics with a half-life of 11.3 hours and only minor accumulation over the week-long treatment period (mycophenolic acid AUC of 12,594 h × ng/mL); however, this standard dosing regimen proved poorly tolerated, with all horses developing bone marrow suppression and elevated bilirubin by Day 7, alongside concerning gastrointestinal effects including reduced appetite, decreased motility, diminished faecal output, and Salmonella shedding in two horses. Before considering MMF for clinical use in equine practice, substantially lower doses, reduced dosing frequency, or both will be necessary to avoid these adverse effects, with any therapeutic trial requiring close haematologic and biochemical monitoring alongside rigorous biosecurity measures to prevent Salmonella transmission.
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Practical Takeaways
- •MMF at 10 mg/kg q12h is not tolerable for horses; lower doses or longer dosing intervals must be investigated before considering this drug for clinical use
- •If MMF is used experimentally in equine practice, implement intensive monitoring including frequent hemograms, biochemistry panels, and strict biosecurity to detect myelosuppression and secondary infections early
- •Be prepared for gastrointestinal side effects (hyporexia, decreased motility, colic risk) and monitor fecal output closely if pursuing MMF therapy in horses
Key Findings
- •MMF at 10 mg/kg PO q12h for 7 days produced mycophenolic acid AUC0-12 of 12,594 h × ng/mL with terminal half-life of 11.3 hours, causing minor metabolite accumulation
- •All 6 horses developed myelosuppression, hyperbilirubinemia, hyporexia, and decreased gastrointestinal motility by day 7 of treatment
- •Salmonellosis was detected in 2 of 6 horses by day 7, indicating potential secondary infection risk
- •Current dosing regimen resulted in unacceptable hematologic and clinical toxicity within one week, necessitating dose/frequency reduction