2016 ACVIM Forum Research Abstract Program

Despite low oral absorption, these data allow for simulation of oral dosage regimens that could be explored in clinical studies. Two regimens can be considered to maintain targeted trough concentrations of 0.5-0.7 µg/mL: 1) 30 mg/kg PO loading dose followed by 15 mg/kg q 48 hours, or 2) 15 mg/kg PO loading dose followed by 7.5 mg/kg q 24 hours. Mycophenolic acid (MPA) is the active moiety of the prodrug mycophenolate mofetil (MMF). It is a selective non-competitive inhibitor of inosine-5ʹ-monophosphate dehydrogenase. MPA is an attractive immunosuppressant option in veterinary medicine due to its rapid onset and commercial availability in multiple formulations. Although MPA is used routinely in humans and canines, there is a paucity of literature supporting MPA's use in feline patients, likely from cats' limited ability to glucuronidate certain medications. Our goal for this study was to evaluate the pharmacokinetics, pharmacodynamics, and safety of MPA in 9 healthy cats. The pharmacokinetics of MPA was evaluated following an intravenous infusion of 5 mg/kg (n = 2) and 10 mg/kg (n = 1) of MMF (CellCeptÒ intravenous, Roche Lab Inc.) Surprisingly, the plasma concentration of MPA in cats at these doses were remarkably low compared with the plasma levels consistent with immunosuppressive levels in humans. Therefore, we evaluated the PK of MPA using 20 mg/kg of MMF administered twice 12 hs apart (n = 6). Following the infusion, all cats metabolized MMF into MPA. The maximum observed MPA plasma concentration ranged between 3.4 and 22 µg/mL after the first dose and between 6.7 and 20 µg/ mL, following the second dose. The evaluation of the concentration time profile of MPA in plasma revealed additional peaks of MPA which could correspond to enterohepatic recycling of MPA.