CPC A61K 31/365 (2013.01) [A61K 9/167 (2013.01); A61K 9/2072 (2013.01); A61K 9/5078 (2013.01); A61K 31/343 (2013.01); A61P 37/02 (2018.01); A61P 37/06 (2018.01); A61K 9/2027 (2013.01); A61K 9/2054 (2013.01); A61K 9/4808 (2013.01)] | 20 Claims |
1. A method for suppressing lymphocyte proliferation in a canine subject, comprising orally administering to the canine subject a single dose of a controlled-release composition per day for 15 or more days, wherein the controlled-release formulation comprises a multiparticulate drug delivery system (MDDS) containing a plurality of particulate subunits that each comprise:
i) a core having a diameter 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;
iv) a protective layer comprising a methacrylate-based polymer disposed over the controlled-release layer; and
achieving an average plasma [MPA] of about 250 ng/ml to about 3000 ng/ml over about 8 hours following a first dose of the controlled-release formulation,
whereupon at 2.5 hours, 4 hours, and 8 hours following the first dose, a percentage of proliferating lymphocytes in a whole blood sample from the subject is reduced by least about 35% as compared to a pre-dose percentage of proliferating lymphocytes in a whole blood sample obtained from the subject 15 or fewer minutes prior to the first dose, as determined using monoclonal antibody Ki-67, and the percentage of proliferating lymphocytes in the whole blood sample from the canine subject is lower than the 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
wherein over the 15 days, the canine subject exhibits a reduced number, a reduced severity, or both, of adverse gastrointestinal events as compared to the reference canine subject that received the immediate-release formulation comprising a MPA active agent, wherein the adverse gastrointestinal event is selected from the group consisting of emesis, diarrhea, and soft stool.
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