Mycophenolic Acid (MPA) and Metabolite

Mycophenolic acid (MPA) is the active metabolite of the prodrug, mycophenolate mofetil (MMF). Absorption of the prodrug is rapid following oral administration to the extent that detectable levels are not seen. Similar effects are observed after cessation of IV administration. Once formed, MPA undergoes metabolism to form the pharmacologically inactive phenolic glucuronide metabolite, MPAG. In vivo, MPAG is converted to MPA via enterohepatic recirculation, which results in a secondary peak in the plasma concentration time profile.¹ MPA and MPAG are 92% and 87% protein bound, respectively, at usual clinical concentrations.

Recent reports have suggested that there could be a potential pharmacokinetic drug interaction between MPA and the calcineurin inhibitors. Several groups have observed that, in combination with cyclosporine, MPA serum concentrations are lower, and the MPAG serum concentrations are higher than in combination with tacrolimus.¹

MPA has also been implicated as an adjuvant with highly active antiretroviral therapy (HAART) due to the selective inhibition of the conversion of inosine 5′-monophosphate to xanthosine 5′-monophosphate by the enzyme, inosine 5′-monophosphate dehydrogenase (IMPDH). Blocking this enzyme in lymphocytes depletes guanosine triphosphate (GTP) and deoxyguanosine triphosphate (dGTP) pools. This depletion of dGTP pools inhibits the activation of T lymphocytes, thereby limiting the availability of target cells for HIV.²