Vectorial transport of fexofenadine across caco-2 cells: Involvement of apical uptake and basolateral efflux transporters

Molecular Pharmaceutics

Volumn 8, Issue 5, 2011, Pages 1677-1686

  Ming, Xin ^a   Knight, Beverly M ^a,b   Thakker, Dhiren R ^a  

^a University of North Carolina   (United States)

^b TAKEDA PHARMACEUTICALS   (United States)

Author keywords

basolateral efflux; Caco 2 cells; fexofenadine; intestinal absorption; MRP3; OATP2B1

Indexed keywords

FEXOFENADINE; MULTIDRUG RESISTANCE PROTEIN 3; ORGANIC CATION TRANSPORTER 2; VERLUKAST;

ABSORPTION; ANIMAL CELL; ARTICLE; BASOLATERAL MEMBRANE; CELL TRANSPORT; CONTROLLED STUDY; DRUG ABSORPTION; DRUG EFFECT; DRUG TRANSPORT; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IMMUNOLOCALIZATION; MONOLAYER CULTURE; NONHUMAN; PH MEASUREMENT; PRIORITY JOURNAL;

ANIMALS; CACO-2 CELLS; CELL LINE; CELL POLARITY; DOGS; ENTEROCYTES; HISTAMINE H1 ANTAGONISTS, NON-SEDATING; HUMANS; INTESTINAL ABSORPTION; KIDNEY TUBULES, DISTAL; MEMBRANE TRANSPORT MODULATORS; MODELS, BIOLOGICAL; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; ORGANIC ANION TRANSPORTERS; P-GLYCOPROTEIN; PRODRUGS; PROTEIN TRANSPORT; RECOMBINANT PROTEINS; TERFENADINE;

EID: 80053530180     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp200026v     Document Type: Article

References (56)

1. Vazquez, E.; Whitfield, L. Seldane warnings Posit Aware 1997, 8 (6) 12
2. Yasui-Furukori, N.; Uno, T.; Sugawara, K.; Tateishi, T. Different effects of three transporting inhibitors, verapamil, cimetidine, and probenecid, on fexofenadine pharmacokinetics Clin. Pharmacol. Ther. 2005, 77 (1) 17-23 (Pubitemid 40075385)
3. Dresser, G. K.; Kim, R. B.; Bailey, D. G. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides Clin. Pharmacol. Ther. 2005, 77 (3) 170-177 (Pubitemid 40269132)
4. Tian, X.; Zamek-Gliszczynski, M. J.; Li, J.; Bridges, A. S.; Nezasa, K.; Patel, N. J.; Raub, T. J.; Brouwer, K. L. Multidrug resistance-associated protein 2 is primarily responsible for the biliary excretion of fexofenadine in mice Drug Metab. Dispos. 2008, 36 (1) 61-64
5. Matsushima, S.; Maeda, K.; Hayashi, H.; Debori, Y.; Schinkel, A. H.; Schuetz, J. D.; Kusuhara, H.; Sugiyama, Y. Involvement of multiple efflux transporters in hepatic disposition of fexofenadine Mol. Pharmacol. 2008, 73 (5) 1474-1483 (Pubitemid 351574837)
6. Tian, X.; Swift, B.; Zamek-Gliszczynski, M. J.; Belinsky, M. G.; Kruh, G. D.; Brouwer, K. L. Impact of basolateral multidrug resistance-associated protein (Mrp) 3 and Mrp4 on the hepatobiliary disposition of fexofenadine in perfused mouse livers Drug Metab. Dispos. 2008, 36 (5) 911-915 (Pubitemid 351574889)
7. Tahara, H.; Kusuhara, H.; Fuse, E.; Sugiyama, Y. P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion Drug Metab. Dispos. 2005, 33 (7) 963-968 (Pubitemid 41002778)
8. Cvetkovic, M.; Leake, B.; Fromm, M. F.; Wilkinson, G. R.; Kim, R. B. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine Drug Metab. Dispos. 1999, 27 (8) 866-871 (Pubitemid 29347585)
9. Chen, C.; Hanson, E.; Watson, J. W.; Lee, J. S. P-Glycoprotein limits the brain penetration of nonsedating but not sedating H1-antagonists Drug Metab. Dispos. 2003, 31 (3) 312-318 (Pubitemid 36249686)
10. Polli, J. W.; Baughman, T. M.; Humphreys, J. E.; Jordan, K. H.; Mote, A. L.; Salisbury, J. A.; Tippin, T. K.; Serabjit-Singh, C. J. P-Glycoprotein influences the brain concentrations of cetirizine (Zyrtec), a second-generation nonsedating antihistamine J. Pharm. Sci. 2003, 92 (10) 2082-2089 (Pubitemid 37175638)
11. Petri, N.; Tannergren, C.; Rungstad, D.; Lennernas, H. Transport characteristics of fexofenadine in the Caco-2 cell model Pharm. Res. 2004, 21 (8) 1398-1404 (Pubitemid 39149654)
12. Tahara, H.; Kusuhara, H.; Maeda, K.; Koepsell, H.; Fuse, E.; Sugiyama, Y. Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid Drug Metab. Dispos. 2006, 34 (5) 743-747
13. Shimizu, M.; Uno, T.; Sugawara, K.; Tateishi, T. Effects of itraconazole and diltiazem on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein Br. J. Clin. Pharmacol. 2006, 61 (5) 538-544
14. Tannergren, C.; Knutson, T.; Knutson, L.; Lennernas, H. The effect of ketoconazole on the in vivo intestinal permeability of fexofenadine using a regional perfusion technique Br. J. Clin. Pharmacol. 2003, 55 (2) 182-190 (Pubitemid 36237864)
15. Tannergren, C.; Petri, N.; Knutson, L.; Hedeland, M.; Bondesson, U.; Lennernas, H. Multiple transport mechanisms involved in the intestinal absorption and first-pass extraction of fexofenadine Clin. Pharmacol. Ther. 2003, 74 (5) 423-436 (Pubitemid 37357721)
16. Dresser, G. K.; Bailey, D. G.; Leake, B. F.; Schwarz, U. I.; Dawson, P. A.; Freeman, D. J.; Kim, R. B. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine Clin. Pharmacol. Ther. 2002, 71 (1) 11-20 (Pubitemid 34124034)
17. Satoh, H.; Yamashita, F.; Tsujimoto, M.; Murakami, H.; Koyabu, N.; Ohtani, H.; Sawada, Y. Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B Drug Metab. Dispos. 2005, 33 (4) 518-523 (Pubitemid 40393194)
18. Nozawa, T.; Suzuki, M.; Takahashi, K.; Yabuuchi, H.; Maeda, T.; Tsuji, A.; Tamai, I. Involvement of estrone-3-sulfate transporters in proliferation of hormone-dependent breast cancer cells J. Pharmacol. Exp. Ther. 2004, 311 (3) 1032-1037 (Pubitemid 39612708)
19. Shimizu, M.; Fuse, K.; Okudaira, K.; Nishigaki, R.; Maeda, K.; Kusuhara, H.; Sugiyama, Y. Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans Drug Metab. Dispos. 2005, 33 (10) 1477-1481 (Pubitemid 41323995)
20. Tamai, I.; Nezu, J.; Uchino, H.; Sai, Y.; Oku, A.; Shimane, M.; Tsuji, A. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family Biochem. Biophys. Res. Commun. 2000, 273 (1) 251-260 (Pubitemid 30426895)
21. Hilgendorf, C.; Ahlin, G.; Seithel, A.; Artursson, P.; Ungell, A. L.; Karlsson, J. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines Drug Metab. Dispos. 2007, 35 (8) 1333-1340 (Pubitemid 47121774)
22. Meier, Y.; Eloranta, J. J.; Darimont, J.; Ismair, M. G.; Hiller, C.; Fried, M.; Kullak-Ublick, G. A.; Vavricka, S. R. Regional distribution of solute carrier mRNA expression along the human intestinal tract Drug Metab. Dispos. 2007, 35 (4) 590-594 (Pubitemid 46513261)
23. Petri, N.; Borga, O.; Nyberg, L.; Hedeland, M.; Bondesson, U.; Lennernas, H. Effect of erythromycin on the absorption of fexofenadine in the jejunum, ileum and colon determined using local intubation in healthy volunteers Int. J. Clin. Pharmacol. Ther. 2006, 44 (2) 71-79 (Pubitemid 43230589)
24. Kobayashi, D.; Nozawa, T.; Imai, K.; Nezu, J.; Tsuji, A.; Tamai, I. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane J. Pharmacol. Exp. Ther. 2003, 306 (2) 703-708 (Pubitemid 36886171)
25. Muller, J.; Lips, K. S.; Metzner, L.; Neubert, R. H.; Koepsell, H.; Brandsch, M. Drug specificity and intestinal membrane localization of human organic cation transporters (OCT) Biochem. Pharmacol. 2005, 70 (12) 1851-1860 (Pubitemid 41612016)
26. Elimrani, I.; Lahjouji, K.; Seidman, E.; Roy, M. J.; Mitchell, G. A.; Qureshi, I. Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells Am. J. Physiol. Gastrointest. Liver Physiol. 2003, 284 (5) G863-G871
27. Koepsell, H.; Lips, K.; Volk, C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications Pharm. Res. 2007, 24 (7) 1227-1251 (Pubitemid 46876495)
28. Cheeseman, C. Role of intestinal basolateral membrane in absorption of nutrients Am. J. Physiol. 1992, 263 (3 Pt 2) R482-R488
29. Ballatori, N.; Christian, W. V.; Lee, J. Y.; Dawson, P. A.; Soroka, C. J.; Boyer, J. L.; Madejczyk, M. S.; Li, N. OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia Hepatology 2005, 42 (6) 1270-1279 (Pubitemid 43260029)
30. Rao, A.; Haywood, J.; Craddock, A. L.; Belinsky, M. G.; Kruh, G. D.; Dawson, P. A. The organic solute transporter alpha-beta, Ostalpha-Ostbeta, is essential for intestinal bile acid transport and homeostasis Proc. Natl. Acad. Sci. U.S.A 2008, 105 (10) 3891-3896 (Pubitemid 351723495)
31. Wang, W.; Seward, D. J.; Li, L.; Boyer, J. L.; Ballatori, N. Expression cloning of two genes that together mediate organic solute and steroid transport in the liver of a marine vertebrate Proc. Natl. Acad. Sci. U.S.A 2001, 98 (16) 9431-9436 (Pubitemid 32743934)
32. Seward, D. J.; Koh, A. S.; Boyer, J. L.; Ballatori, N. Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta J. Biol. Chem. 2003, 278 (30) 27473-27482 (Pubitemid 36899930)
33. Deeley, R. G.; Westlake, C.; Cole, S. P. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins Physiol. Rev. 2006, 86 (3) 849-899 (Pubitemid 44033384)
34. Zimmermann, C.; Gutmann, H.; Hruz, P.; Gutzwiller, J. P.; Beglinger, C.; Drewe, J. Mapping of multidrug resistance gene 1 and multidrug resistance-associated protein isoform 1 to 5 mRNA expression along the human intestinal tract Drug Metab. Dispos. 2005, 33 (2) 219-224 (Pubitemid 40216589)
35. Prime-Chapman, H. M.; Fearn, R. A.; Cooper, A. E.; Moore, V.; Hirst, B. H. Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells J. Pharmacol. Exp. Ther. 2004, 311 (2) 476-484 (Pubitemid 39391531)
36. Mottino, A. D.; Hoffman, T.; Jennes, L.; Vore, M. Expression and localization of multidrug resistant protein mrp2 in rat small intestine J. Pharmacol. Exp. Ther. 2000, 293 (3) 717-723 (Pubitemid 30417835)
37. Rost, D.; Mahner, S.; Sugiyama, Y.; Stremmel, W. Expression and localization of the multidrug resistance-associated protein 3 in rat small and large intestine Am. J. Physiol. Gastrointest. Liver Physiol. 2002, 282 (4) G720-G726
38. van Aubel, R. A.; Smeets, P. H.; Peters, J. G.; Bindels, R. J.; Russel, F. G. The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP J. Am. Soc. Nephrol. 2002, 13 (3) 595-603 (Pubitemid 34183923)
39. Rius, M.; Nies, A. T.; Hummel-Eisenbeiss, J.; Jedlitschky, G.; Keppler, D. Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane Hepatology 2003, 38 (2) 374-384 (Pubitemid 36919858)
40. Ming, X.; Thakker, D. R. Role of basolateral efflux transporter MRP4 in the intestinal absorption of the antiviral drug adefovir dipivoxil Biochem. Pharmacol. 2010, 79 (3) 455-462
41. Schmiedlin-Ren, P.; Thummel, K. E.; Fisher, J. M.; Paine, M. F.; Lown, K. S.; Watkins, P. B. Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin D3 Mol. Pharmacol. 1997, 51 (5) 741-754 (Pubitemid 27224679)
42. Ming, X.; Ju, W.; Wu, H.; Tidwell, R. R.; Hall, J. E.; Thakker, D. R. Transport of dicationic drugs pentamidine and furamidine by human organic cation transporters Drug Metab. Dispos. 2009, 37 (2) 424-430
43. Mouly, S. J.; Paine, M. F.; Watkins, P. B. Contributions of CYP3A4, P-glycoprotein, and serum protein binding to the intestinal first-pass extraction of saquinavir J. Pharmacol. Exp. Ther. 2004, 308 (3) 941-948 (Pubitemid 38263969)
44. Bourdet, D. L.; Thakker, D. R. Saturable absorptive transport of the hydrophilic organic cation ranitidine in Caco-2 cells: role of pH-dependent organic cation uptake system and P-glycoprotein Pharm. Res. 2006, 23 (6) 1165-1177 (Pubitemid 43946139)
45. Gan, L. S. L.; Thakker, D. R. Applications of the Caco-2 model in the design and development of orally active drugs: Elucidation of biochemical and physical barriers posed by the intestinal epithelium Adv. Drug Deliv. Rev. 1997, 23 (1-3) 77-98 (Pubitemid 27046995)
46. Scheffer, G. L.; Kool, M.; Heijn, M.; de Haas, M.; Pijnenborg, A. C.; Wijnholds, J.; van Helvoort, A.; de Jong, M. C.; Hooijberg, J. H.; Mol, C. A.; van der Linden, M.; de Vree, J. M.; van der Valk, P.; Elferink, R. P.; Borst, P.; Scheper, R. J. Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-glycoprotein with a panel of monoclonal antibodies Cancer Res. 2000, 60 (18) 5269-5277
47. Glaeser, H.; Bailey, D. G.; Dresser, G. K.; Gregor, J. C.; Schwarz, U. I.; McGrath, J. S.; Jolicoeur, E.; Lee, W.; Leake, B. F.; Tirona, R. G.; Kim, R. B. Intestinal drug transporter expression and the impact of grapefruit juice in humans Clin. Pharmacol. Ther. 2007, 81 (3) 362-370 (Pubitemid 46364477)
48. Nozawa, T.; Imai, K.; Nezu, J.; Tsuji, A.; Tamai, I. Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human J. Pharmacol. Exp. Ther. 2004, 308 (2) 438-445 (Pubitemid 38134202)
49. Daniel, H.; Neugebauer, B.; Kratz, A.; Rehner, G. Localization of acid microclimate along intestinal villi of rat jejunum Am. J. Physiol. 1985, 248 (3 Pt 1) G293-G298
50. Dawson, P. A.; Hubbert, M.; Haywood, J.; Craddock, A. L.; Zerangue, N.; Christian, W. V.; Ballatori, N. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter J. Biol. Chem. 2005, 280 (8) 6960-6968 (Pubitemid 40341252)
51. Gekeler, V.; Ise, W.; Sanders, K. H.; Ulrich, W. R.; Beck, J. The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance Biochem. Biophys. Res. Commun. 1995, 208 (1) 345-352
52. Chen, Z. S.; Kawabe, T.; Ono, M.; Aoki, S.; Sumizawa, T.; Furukawa, T.; Uchiumi, T.; Wada, M.; Kuwano, M.; Akiyama, S. I. Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter Mol. Pharmacol. 1999, 56 (6) 1219-1228
53. Zeng, H.; Chen, Z. S.; Belinsky, M. G.; Rea, P. A.; Kruh, G. D. Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport Cancer Res. 2001, 61 (19) 7225-7232 (Pubitemid 32946519)
54. Reid, G.; Wielinga, P.; Zelcer, N.; De Haas, M.; Van Deemter, L.; Wijnholds, J.; Balzarini, J.; Borst, P. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5 Mol. Pharmacol. 2003, 63 (5) 1094-1103 (Pubitemid 36529928)
55. Letschert, K.; Komatsu, M.; Hummel-Eisenbeiss, J.; Keppler, D. Vectorial transport of the peptide CCK-8 by double-transfected MDCKII cells stably expressing the organic anion transporter OATP1B3 (OATP8) and the export pump ABCC2 J. Pharmacol. Exp. Ther. 2005, 313 (2) 549-556 (Pubitemid 40604153)
56. Mouly, S.; Paine, M. F. P-glycoprotein increases from proximal to distal regions of human small intestine Pharm. Res. 2003, 20 (10) 1595-1599 (Pubitemid 37268274)