The impact of P-glycoprotein and Mrp2 on mycophenolic acid levels in mice.
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Wang J, Figurski M, Shaw LM, Burckart GJ
The impact of P-glycoprotein and Mrp2 on mycophenolic acid levels in mice.
Transpl Immunol. 2008 Jul;19(3-4):192-6. doi: 10.1016/j.trim.2008.05.009. Epub 2008 Jun 18.
- PubMed ID
- 18586494 [ View in PubMed]
- Abstract
Considerable variability has been observed in the exposure to mycophenolic acid (MPA) in transplant patients. The objective of this study was to clarify the roles of two important transporters, P-gp and Mrp2, in MPA absorption using an in vivo model. FVB strain wild-type, Mdr1a/1b(-/-) and Mrp2(-/-) mice were subjected to the administration of mycophenolate mofetil (MMF) alone or MMF in combination with cyclosporine (CsA), an immunosuppressive inhibitor of P-gp and Mrp2. At 30 min following treatment, the MPA levels in Mdr1a/1b(-/-) and Mrp2(-/-) mice were markedly increased as compared to wild-type mice. In contrast to the reduced MPA concentrations observed at 60 and 120 min in the CsA-treated groups, CsA produced increased mycophenolate glucuronide (MPAG) plasma levels in CsA-treated mice at each sampling time. Brain concentrations of MPA were elevated in the Mdr1a/1b(-/-) mice at 30 min after MMF in conjunction with increased plasma MPA concentrations, but not in the wild-type or the Mrp2(-/-) mice. This study demonstrated that: a) MPA appears to be a substrate for P-gp, and b) MPA plasma concentrations are influenced by multiple membrane transporters. Drug-transporter interactions must be considered in patients receiving mycophenolic acid products.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Mycophenolate mofetil Canalicular multispecific organic anion transporter 1 Protein Humans UnknownNot Available Details Mycophenolate mofetil P-glycoprotein 1 Protein Humans UnknownSubstrateDetails