Skip to Main content Skip to Navigation
Journal articles

The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics.

Abstract : The goal of this study was to determine the roles of the organic anion-transporting polypeptides (OATPs) OATP1A2, OATP1B1, and OATP1B3 and their genetic variants in the pharmacokinetics of the immunosuppressive drug mycophenolate mofetil (MMF). Using OATP-transfected human embryonic kidney (HEK) cells, we measured the uptake of mycophenolic acid (MPA) and its glucuronide (MPAG). MPAG, but not MPA, significantly accumulated in cells expressing OATP1B3 or OATP1B1 (P < 0.05). The pharmacokinetics of both MPA and MPAG were significantly influenced by the OATP1B3 polymorphism 334T>G/699G>A in 70 renal transplant patients receiving combination treatment of MMF with either tacrolimus or sirolimus, but not in 115 patients receiving MMF and cyclosporine. The decrease in dose-normalized (dn) MPA exposure and the concomitant increase in the MPAG/MPA metabolic ratio are consistent with reduced enterohepatic cycling in patients carrying the OATP1B3 334G-699A haplotype. Further studies demonstrated that this variant of OATP1B3 exhibited a reduced maximal velocity (V(max)) in transfected HEK cells, thereby providing functional evidence to support our clinical findings.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00415314
Contributor : Pierre Marquet <>
Submitted on : Friday, May 7, 2010 - 12:13:00 PM
Last modification on : Thursday, August 8, 2019 - 3:50:27 PM
Long-term archiving on: : Thursday, September 16, 2010 - 12:35:21 PM

Identifiers

Collections

Citation

Nicolas Picard, Sook Wah Yee, Jean-Baptiste Woillard, Yvon Lebranchu, Yannick Le Meur, et al.. The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics.. Clinical Pharmacology and Therapeutics, American Society for Clinical Pharmacology and Therapeutics, 2010, 87 (1), pp.100-8. ⟨10.1038/clpt.2009.205⟩. ⟨inserm-00415314⟩

Share

Metrics

Record views

283

Files downloads

1097