Pharmacokinetics of mycophenolate mofetil following single-dose intravenous and single-and multiple-dose oral administration and clinicopathologic effects of mycophenolate mofetil following long-term oral administration in healthy horses

Heather K. Knych, Daniel S. McKemie, Kirsten L. Kanarr, Stephen D. White

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmaco-kinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses. ANIMALS 12 healthy adult horses. PROCEDURES In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg, PO, q 48 h for an additional 30 days). RESULTS Following IV (single-dose) or PO (single-or multiple-dose) administra-tion, MMF was rapidly converted to mycophenolic acid. For single-dose PO administration, mean ± SD maximum plasma mycophenolic acid con-centration was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours. For single-dose IV administration, mean systemic clearance and volume of distribution at steady state were 0.689 ± 0.194 L/h/kg and 1.57 ± 0.626 L/kg, respectively. Following single doses, mean terminal half-life was 3.99 ± 0.865 hours for IV administration and 4.02 ± 1.01 hours for PO administration. The accumula-tion index following long-term PO administration was 1.0 ± 0.002, and the terminal half-life was 4.59 ± 1.25 hours following the final dose on day 60. None of the horses developed abnormal clinical signs or had any consis-tently abnormal clinicopathologic findings. CONCLUSIONS AND CLINICAL RELEVANCE Further investigation of the clinical efficacy of long-term MMF treatment of horses with autoimmune diseases is warranted.

Original languageEnglish (US)
Pages (from-to)502-509
Number of pages8
JournalAmerican journal of veterinary research
Volume82
Issue number6
DOIs
StatePublished - Jun 2021

ASJC Scopus subject areas

  • veterinary(all)

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