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J Vet Intern Med. 2019 Sep;33(5):2020-2028. doi: 10.1111/jvim.15585. Epub 2019 Aug 19.

Pharmacokinetics of mycophenolic acid and its effect on CD4+ and CD8+ T cells after oral administration of mycophenolate mofetil to healthy cats.

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1
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington.

Abstract

BACKGROUND:

Mycophenolate mofetil (MMF) is an immunosuppressant used in human and veterinary medicine. Little pharmacokinetic and pharmacodynamic information on MMF is available in cats.

OBJECTIVE:

To evaluate the plasma disposition of mycophenolic acid (MPA) and assess its effect on total peripheral blood mononuclear cells and CD4+ /CD8+ ratios after PO administration of MMF.

ANIMALS:

Healthy cats (n = 10).

METHODS:

Mycophenolate mofetil was administered at a dosage of 10 mg/kg q12h (n = 3), 15 mg/kg q12h (n = 3), and 15 mg/kg q8h (n = 4) for 7 days. Concentrations of MPA and derivatives were determined using ultra-high-performance liquid chromatography. Flow cytometry was used to assess CD4+ /CD8+ T-cell ratios.

RESULTS:

All cats biotransformed MMF into MPA. Half of the cats (5/10) had adverse effects within 1 week of MMF administration. Area under the curve limit of quantification (AUC0-LOQh ) of MPA ranged from 1.27 to 2.03 hours·μg/mL and from 1.77 to 8.54 hours·μg/mL after the first and last PO dose of 10 mg/kg. The AUC0-loqh of MPA ranged from 2.18 to 31 hours·μg/mL after the first dose of 15 mg/kg of MMF. Before the first dose of MMF, the average total number of PBMC ranged from 1.2 to 9.3 million/mL. At the last dose of MMF, the average total number of PBMC ranged from 3 to 5 million/mL.

CONCLUSION:

Mycophenolic acid was detected in all cats. The dose 10 mg/kg given q12h for 1 week was tolerated (n = 3). The efficacy of MMF as an immunosuppressant and long-term safety in cats of this dosage regimen is unknown.

KEYWORDS:

cats; immunosuppressant; mycophenolate mofetil; pharmacodynamics; pharmacokinetics

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