mycophenolic

Mycophenolic acid (MPA) is a secondary metabolite produced by several Penicillium and Aspergillus species. It is the active component of the immunosuppressive drugs mycophenolate mofetil (MMF) and mycophenolate sodium (EC-MPS). The term mycophenolic may refer to the acid itself or to its prodrug forms used in clinical practice.

MPA inhibits inosine monophosphate dehydrogenase (IMPDH), particularly the type II isoform common in activated lymphocytes. By blocking de novo guanine nucleotide synthesis, it preferentially suppresses the proliferation of T and B lymphocytes, yielding immunosuppressive effects with a cytostatic rather than cytotoxic profile.

In transplantation, MPA is used to prevent rejection in kidney, heart, and liver transplants as part of regimens with calcineurin inhibitors and corticosteroids. It is also employed in certain autoimmune diseases and is used for graft-versus-host disease prophylaxis in allogeneic stem cell transplantation.

MPA is supplied as prodrugs: MMF and EC-MPS. After administration, MMF is hydrolyzed to MPA; MPA is further glucuronidated to MPAG in the liver. MPAG and MPA undergo enterohepatic recirculation, contributing to the drug’s exposure profile. Absorption, bioavailability, and clearance vary with formulation and coadministered drugs, and hepatic metabolism with renal excretion are the primary routes of elimination.

Common adverse effects include gastrointestinal symptoms (diarrhea, nausea, abdominal pain) and hematologic effects (leukopenia, anemia, thrombocytopenia). Immunosuppressed patients have an increased risk of infections. Pregnancy carries significant risks, and the drug is typically avoided during pregnancy. Concomitant medications can alter MPA exposure, notably certain bile acid sequestrants and some immunosuppressants.