Clinical pharmacokinetic interaction: tacrolimus and mycophenolate mofetil

The clinical pharmacokinetic interaction between tacrolimus and mycophenolate mofetil (MMF) is a critical pharmacological phenomenon in solid organ transplantation. Tacrolimus, a calcineurin inhibitor, and MMF, a prodrug of mycophenolic acid (MPA), are frequently co-administered to prevent graft rejection (PMID: 15504145). Unlike cyclosporine, tacrolimus does not inhibit the multidrug resistance-associated protein 2 (MRP2) transporter, which is responsible for the biliary excretion of mycophenolic acid glucuronide (MPAG) (PMID: 12130734). This allows MPAG to reach the intestine, where it is converted back to MPA by bacterial enzymes and reabsorbed, a process known as enterohepatic recirculation. Consequently, patients receiving tacrolimus exhibit significantly higher MPA plasma concentrations (AUC) compared to those on cyclosporine-based regimens (PMID: 11588301). This interaction is not a biological target itself but a complex drug-drug interaction that necessitates therapeutic drug monitoring to balance immunosuppressive efficacy against the risk of toxicities such as myelosuppression and gastrointestinal distress (StatPearls: Mycophenolate Mofetil).

Other names

Tacrolimus-mycophenolate interactionTacrolimus-MMF interactionFK506-MPA interaction

Tacrolimus does not inhibit the multidrug resistance-associated protein 2 (MRP2)-mediated biliary excretion of mycophenolic acid glucuronide (MPAG), unlike cyclosporine, which allows for the enterohepatic recirculation of mycophenolic acid (MPA).