Methods and compositions for delivering mycophenolic acid active agents to non-human mammals

A pharmaceutical formulation comprising a plurality of particulate subunits, each of which comprises:

• i) a core having a diameter of less than about 3 mm;
• ii) an active layer disposed over at least a portion of the core and comprising a mycophenolic acid (MPA) active agent, wherein the MPA active agent is sodium mycophenolate;
• iii) a controlled-release layer disposed over the active layer;
• and
• iv) a protective layer comprising a methacrylate-based polymer disposed over the controlled-release layer;
• wherein the pharmaceutical formulation, when first orally administered to a canine, achieves an average plasma [MPA] of about 250 ng/ml to about 3000 ng/ml over about 8 hours following a first dose of the formulation;
• wherein at 2.5 hours, 4 hours, and 8 hours following the first oral administration reduces the percentage of proliferating lymphocytes in a whole blood sample of the canine by least about 35% as compared to a pre-dose percentage of proliferating lymphocytes in a whole blood sample obtained from the canine 15 or fewer minutes prior to the first dose as determined using monoclonal antibody Ki-67;
• which reduced percentage of proliferating lymphocytes in the whole blood sample is lower than a percentage of proliferating lymphocytes in a whole blood sample obtained from a reference canine subject that received an immediate-release formulation comprising a MPA active agent;
• and
• which drug delivery system, when delivered daily to a canine for at least 15 days, reduces the number, severity, or both of adverse gastrointestinal events as compared to a reference canine subject that received the immediate-release formulation comprising a MPA active agent, wherein the adverse gastrointestinal event is emesis, diarrhea, or soft stool.