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

健康猫口服霉酚酸酯后霉酚酸的药代动力学及其对 CD4+ 和 CD8+ T 细胞的影响

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作者:Jennifer E Slovak, Julianne K Hwang, Sol M Rivera, Nicolas F Villarino

Background

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

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.

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.

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).

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.

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