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	Unknown	Not Available	Details
Mycophenolate mofetil	P-glycoprotein 1	Protein	Humans	Unknown	Substrate	Details