The immunosuppressant Mycophenolate mofetil (MMF) has recently gained popularity in veterinary medicine. MMF is a pro-drug for the active moiety mycophenolic acid (MPA), a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). IMPDH inhibition, ultimately leads to suppressed lymphocyte proliferation.
The goal in this study was to evaluate the pharmacodynamics (PD) of MPA after 1 week of varying oral doses of MMF in 10 healthy cats. The PD of MPA was evaluated following oral administration of MMF 10mg/kg PO BID (n=3), 15mg/kg PO BID (n=3), and 15mg/kg PO TID (n=4) for up to 1 week in 10 cats. Blood samples were taken prior to the first administration of MMF, 24 hours into treatment, at day 7 and 12 hours after the last oral dose of MMF.
Isolation of peripheral blood mononuclear cells (PBMC) was performed using standard methods after each blood draw. All samples were cryopreserved and later thawed for subsequent flow cytometry and analyzed in 1 batch. Percentage of positively stained cells for CD4+ and CD8+ antibody were determined by flow cytometry.
Total isolated PBMC numbers were variable in all cats tested at pre-medication, after initiation of oral MPA on day 1, day 7, and after 12 hours of the last dose of oral MMF. There was minimal to no change in the average CD4+ and CD8+ lymphocyte counts in the 10mg/kg BID and 15mg/kg BID groups. There was a mild reduction in CD4+ but not CD8+ lymphocytes in cats treated with 15mg/kg TID of MMF. Overall, the CD4+:CD8+ ratios were nearly the same in the 10mg/kg BID, 15mg/kg BID, and 15mg/kg TID treatment groups<./p>
This study describes the PD of multi-day oral administration of MMF in 10 healthy cats. There was little to no change in the CD4+ lymphocyte counts in the 2 BID groups, and a mild reduction in the 15mg/kg TID group. The CD8+ lymphocytes and the CD4+:CD8+ ratios, showed little to no change for all 3 groups. The results of this study did not show an appreciable reduction in T cell suppression. This may be due a short treatment period or due to the presence of un-activated lymphocytes as the cats were healthy. Future studies will evaluate the PD of MPA in clinically affected feline patients receiving MMF.
Assistant Professor of Small Animal Internal Medicine
Washington State University College of Veterinary Medicine
Dr. Slovak is an Assistant Professor of small animal internal medicine at Washington State University. She is a 2003 graduate of Iowa State University's College of Veterinary Medicine. Dr. Slovak was in a mixed animal, equine, then general small animal practice for 7 years before pursuing her specialization in small animal internal medicine. From 2010-2014, she completed her rotating internship, small animal internal medicine residency and Master of Science at Iowa State University. Her current clinical and research interests include recognizing and minimizing pain, anxiety, and discomfort in her clinical patients, as well as investigating novel diagnostics and therapies for immune mediated and inflammatory conditions of the gastrointestinal and hepatobiliary tracts in felines.
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