Mycophenolic acid glucuronide is transported by multidrug resistance-associated protein 2 and this transport is not inhibited by cyclosporine, tacrolimus or sirolimus

Xenobiotica

Volumn 43, Issue 3, 2013, Pages 229-235

  Patel, Chirag G ^a,b   Ogasawara, Ken ^a   Akhlaghi, Fatemeh ^a  

^a UNIVERSITY OF RHODE ISLAND   (United States)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

AcMPAG; Drug interactions; Immunosuppressive agents; MDCK MRP2; MPA; MPAG; Pharmacokinetics; Translocation

Indexed keywords

ACYL MYCOPHENOLIC ACID GLUCURONIDE; CYCLOSPORIN A; DRUG METABOLITE; MULTIDRUG RESISTANCE PROTEIN 2; MYCOPHENOLIC ACID; MYCOPHENOLIC ACID BETA D GLUCURONIDE; RAPAMYCIN; TACROLIMUS; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG ANTAGONISM; DRUG DIFFUSION; DRUG TRANSPORT; GENETIC TRANSFECTION; MDCK CELL; MEMBRANE VESICLE; MICHAELIS MENTEN KINETICS; NONHUMAN; PROTEIN EXPRESSION;

ADENOSINE TRIPHOSPHATE; ANIMALS; BIOLOGICAL TRANSPORT; CELL MEMBRANE; CELL MEMBRANE PERMEABILITY; CYCLOSPORINE; DIFFUSION; DOGS; EPITHELIAL CELLS; GLUCURONIDES; HUMANS; MADIN DARBY CANINE KIDNEY CELLS; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; MYCOPHENOLIC ACID; SIROLIMUS; TACROLIMUS; TRANSPORT VESICLES;

EID: 84873353604     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.3109/00498254.2012.713531     Document Type: Article

References (28)

1. Chen C, Slitt AL, Dieter MZ, Tanaka Y Schefer GL, Klaassen CD. (2005). Up-regulation of Mrp4 expression in kidney of Mrp2-defcient TR-rats. Biochem Pharmacol 70:1088-1095.
2. Chen J, Terada T, Ogasawara K, Katsura T, Inui K. (2008). Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis. Am J Physiol Renal Physiol 295:F247-F252.
3. Davies NM, Grinyó J, Heading R, Maes B, Meier-Kriesche HU, Oellerich M. (2007). Gastrointestinal side efects of mycophenolic acid in renal transplant patients: a reappraisal. Nephrol Dial Transplant 22:2440-2448.
4. Evers R, Kool M, van Deemter L, Janssen H, Calafat J, Oomen LC, Paulusma CC, Oude Elferink RP, Baas F, Schinkel AH, Borst P. (1998). Drug export activity of the human canalicular multispecifc organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA. J Clin Invest 101:1310-1319.
5. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM, Hofmaster KA, Ishikawa T, Keppler D, Kim RB, Lee CA, Niemi M, Polli JW, Sugiyama Y Swaan PW, Ware JA, Wright SH, Yee SW, Zamek-Gliszczynski MJ, Zhang L; International Transporter Consortium. (2010). Membrane transporters in drug development. Nat Rev Drug Discov 9:215-236.
6. Goodman LS, Grosman-Rimon L, Mikuliszyn R. (2006). Carotid sinus pressure changes during push-pull maneuvers. Aviat Space Environ Med 77:921-928.
7. Halloran PF. (2004). Immunosuppressive drugs for kidney transplantation. N Engl J Med 351:2715-2729.
8. Herédi-Szabó K, Glavinas H, Kis E, Méhn D, Báthori G, Veres Z, Kóbori L, von Richter O, Jemnitz K, Krajcsi P. (2009). Multidrug resistance protein 2-mediated estradiol-17beta-D-glucuronide transport potentiation: in vitro-in vivo correlation and species specifcity. Drug Metab Dispos 37:794-801.
9. Hesselink DA, van Hest RM, Mathot RA, Bonthuis F, Weimar W, de Bruin RW, van Gelder T. (2005). Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Am J Transplant 5:987-994.
10. Ho RH, Kim RB. (2005). Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ter 78:260-277.
11. Kalliokoski A, Niemi M. (2009). Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158:693-705.
12. Kobayashi M, Saitoh H, Kobayashi M, Tadano K, Takahashi Y, Hirano T. (2004). Cyclosporin A, but not tacrolimus, inhibits the biliary excretion of mycophenolic acid glucuronide possibly mediated by multidrug resistance-associated protein 2 in rats. J Pharmacol Exp Ter 309:1029-1035.
13. Kuypers DR, Vanrenterghem Y Squifet JP, Mourad M, Abramowicz D, Oellerich M, Armstrong V, Shipkova M, Daems J. (2003). Twelve-month evaluation of the clinical pharmacokinetics of total and free mycophenolic acid and its glucuronide metabolites in renal allograft recipients on low dose tacrolimus in combination with mycophenolate mofetil. Ter Drug Monit 25:609-622.
14. Lévesque E, Benoit-Biancamano MO, Delage R, Couture F, Guillemette C. (2008). Pharmacokinetics of mycophenolate mofetil and its glucuronide metabolites in healthy volunteers. Pharmacogenomics 9:869-879.
15. Lloberas N, Torras J, Cruzado JM, Andreu F, Oppenheimer F, Sánchez-Plumed J, Gentil MÁ, Brunet M, Ekberg H, Grinyó JM; Spanish Pharmacogenetic Symphony Substudy Group. (2011). Infuence of MRP2 on MPA pharmacokinetics in renal transplant recipients-results of the Pharmacogenomic Substudy within the Symphony Study. Nephrol Dial Transplant 26:3784-3793.
16. Naesens M, Kuypers DR, Verbeke K, Vanrenterghem Y. (2006). Multidrug resistance protein 2 genetic polymorphisms infuence mycophenolic acid exposure in renal allograft recipients. Transplantation 82:1074-1084.
17. Neerman MF, Boothe DM. (2003). A possible mechanism of gastrointestinal toxicity posed by mycophenolic acid. Pharmacol Res 47:523-526.
18. Nguyen T, Park JY, Scudiere JR, Montgomery E. (2009). Mycophenolic acid (cellcept and myofortic) induced injury of the upper GI tract. Am J Surg Pathol 33:1355-1363.
19. Patel CG, Akhlaghi F. (2006). High-performance liquid chromatography method for the determination of mycophenolic acid and its acyl and phenol glucuronide metabolites in human plasma. Ter Drug Monit 28:116-122.
20. Picard N, Marquet P. (2004). In vitro study of mycophenolic acid glucuronidation. Drug Metab Dispos 32:1524; author reply 1525.
21. Picard N, Yee SW, Woillard JB, Lebranchu Y Le Meur Y, Giacomini KM, Marquet P. (2010). The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clin Pharmacol Ter 87:100-108.
22. Picard N, Levoir L, Lamoureux F, Yee SW, Giacomini KM, Marquet P. (2011). Interaction of sirolimus and everolimus with hepatic and intestinal organic anion-transporting polypeptide transporters. Xenobiotica 41:752-757.
23. Shaw LM, Nicholls A, Hale M, Armstrong VW, Oellerich M, Yatscof R, Morris RE, Holt DW, Venkataramanan R, Haley J, Halloran P, Ettenger R, Keown P, Morris RG. (1998). Terapeutic monitoring of mycophenolic acid. A consensus panel report. Clin Biochem 31:317-322.
24. Shipkova M, Armstrong VW, Weber L, Niedmann PD, Wieland E, Haley J, Tönshof B, Oellerich M; German Study Group on Mycophenolate Mofetil Terapy in Pediatric Renal Transplant Recipients. (2002). Pharmacokinetics and protein adduct formation of the pharmacologically active acyl glucuronide metabolite of mycophenolic acid in pediatric renal transplant recipients. Ter Drug Monit 24:390-399.
25. Takekuma Y Kakiuchi H, Yamazaki K, Miyauchi S, Kikukawa T, Kamo N, Ganapathy V, Sugawara M. (2007). Diference between pharmacokinetics of mycophenolic acid (MPA) in rats and that in humans is caused by diferent afnities of MRP2 to a glucuronized form. J Pharm Pharm Sci 10:71-85.
26. Westley IS, Brogan LR, Morris RG, Evans AM, Sallustio BC. (2006). Role of Mrp2 in the hepatic disposition of mycophenolic acid and its glucuronide metabolites: efect of cyclosporine. Drug Metab Dispos 34:261-266.
27. Wolf NA, Burckhardt BC, Burckhardt G, Oellerich M, Armstrong VW. (2007). Mycophenolic acid (MPA) and its glucuronide metabolites interact with transport systems responsible for excretion of organic anions in the basolateral membrane of the human kidney. Nephrol Dial Transplant 22:2497-2503.
28. Yamaguchi K, Murai T, Yabuuchi H, Kurosawa T. (2010). Measurement of transport activities of bile acids in human multidrug resistance-associated protein 3 using liquid chromatography-tandem mass spectrometry. Anal Sci 26:317-323.