Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid in Healthy Cats After Twice-Daily Intravenous Infusion of Mycophenolate Mofetil for Three Days

Am J Vet Res. 2018 Oct;79(10):1093-1099. doi: 10.2460/ajvr.79.10.1093.

Abstract

OBJECTIVE To evaluate the plasma disposition of mycophenolic acid (MPA) and its derivatives MPA glucuronide and MPA glucoside after twice-daily infusions of mycophenolate mofetil (MMF) in healthy cats for 3 days and to assess the effect of MMF administration on peripheral blood mononuclear cell (PBMC) counts and CD4+-to-CD8+ ratios. ANIMALS 5 healthy adult cats. PROCEDURES MMF was administered to each cat (10 mg/kg, IV, q 12 h for 3 days). Each dose of MMF was diluted with 5% dextrose in water and then administered over a 2-hour period with a syringe pump. Blood samples were collected for analysis. A chromatographic method was used to quantitate concentrations of MPA and its metabolites. Effects of MMF on PBMC counts and CD4+-to-CD8+ ratios were assessed by use of flow cytometry. RESULTS All cats biotransformed MMF into MPA. The MPA area under the plasma concentration-time curve from 0 to 14 hours ranged from 14.6 to 37.6 mg·h/L and from 14.4 to 22.3 mg·h/L after the first and last infusion, respectively. Total number of PBMCs was reduced in 4 of 5 cats (mean ± SD reduction, 25.9 ± 15.8% and 26.7 ± 19.3%) at 24 and 48 hours after the end of the first infusion of MMF, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Plasma disposition of MPA after twice-daily IV infusions for 3 days was variable in all cats. There were no remarkable changes in PBMC counts and CD4+-to-CD8+ ratios.

MeSH terms

  • Animals
  • Area Under Curve
  • Cats / blood
  • Cats / metabolism*
  • Drug Administration Schedule / veterinary
  • Female
  • Flow Cytometry / veterinary
  • Glucuronides / blood
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / pharmacology*
  • Infusions, Intravenous / veterinary
  • Leukocytes, Mononuclear / drug effects*
  • Male
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / blood
  • Mycophenolic Acid / pharmacokinetics*
  • Mycophenolic Acid / pharmacology*

Substances

  • Glucuronides
  • Immunosuppressive Agents
  • mycophenolic acid glucuronide
  • Mycophenolic Acid