Multidrug resistance-associated protein 2 and Organic anion transporter 3 (MRP2 and OAT3)

Multidrug resistance-associated protein 2 (MRP2, ABCC2) and Organic anion transporter 3 (OAT3, SLC22A8) are essential membrane transporters that regulate the pharmacokinetics of the immunosuppressant mycophenolic acid (MPA) (UniProt, 2024). MRP2 is primarily expressed on the canalicular membrane of hepatocytes, where it facilitates the biliary excretion of mycophenolic acid glucuronide (MPAG), the main metabolite of MPA (PubChem, 2024). OAT3 is located on the basolateral membrane of renal proximal tubule cells and is responsible for the uptake of MPAG from the systemic circulation for renal elimination (PubMed, 2014). Corticosteroids, such as prednisone, are known to induce the expression of these transporters by activating nuclear receptors like the Pregnane X Receptor (PXR) (Kidney International, 2006). This induction increases the clearance of MPAG and can significantly alter the enterohepatic recirculation of MPA, leading to decreased systemic drug exposure (Clinical Pharmacokinetics, 1998). Such interactions are clinically critical in transplant medicine, as they can reduce the efficacy of immunosuppressive therapy and increase the risk of organ rejection (NIH, 2023). Consequently, therapeutic drug monitoring of MPA levels is often required when corticosteroid dosages are adjusted (PubMed, 2006).

Other names

ABCC2SLC22A8Canalicular multispecific organic anion transporter 1cMOATOrganic anion transporter 3

Corticosteroids act as transcriptional inducers of the ABCC2 (MRP2) and SLC22A8 (OAT3) genes, primarily through the activation of nuclear receptors such as the Pregnane X Receptor (PXR), which increases the transport capacity for mycophenolic acid and its glucuronide metabolites.