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

Jennifer E Slovak, Julianne K Hwang, Sol M Rivera, Nicolas F Villarino
Journal of Veterinary Internal Medicine 2019 August 19

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. Peripheral blood mononuclear cell counts were variable in all cats (range, 1.2-9.3 × 106 /mL) and were end-dose (range, 3-5 × 106 /mL). Little change was noted in CD4+ /CD8+ ratios (range, 1-5.56 pre-dose; 1.1-2.66 end-dose).

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.

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