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Transporters in the intestine limiting drug and toxin absorption

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Abstract

The pharmacokinetic behaviour of drugs strongly depends on transporters in intestine and liver. The extent of absorption in the intestine depends on diffusion across the mucosa as well as transporter-mediated uptake across the apical membrane of enterocytes. Efflux pumps in this membrane may strongly reduce the extent of net uptake. These efflux pumps are ATP-binding cassette (ABC) transporters which are also expressed in the apical membrane of the hepatocyte were they mediate excretion into bile. This combined activity strongly determines whether drugs have access to the systemic circulation.

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References

  1. Anapolsky, A., Teng, S., Dixit, S., and Piquette-Miller, M. (2006):Drug Metab. Dispos,34, 405–409.

    CAS  PubMed  Google Scholar 

  2. Bakos, E., Evers, R., Sinko, E., Varadi, A., Borst, P., and Sarkadi, B. (2000):Mol. Pharmacol.,57, 760–768.

    CAS  PubMed  Google Scholar 

  3. Bodo, A., Bakos, E., Szeri, F., Varadi, A., and Sarkadi, B. (2003):J. Biol. Chem.,278, 23529–23537.

    Article  CAS  PubMed  Google Scholar 

  4. Borst, P., Zelcer, N., and van de Wetering, K. (2006):Cancer Lett.,234, 51–61.

    Article  CAS  PubMed  Google Scholar 

  5. Clark, R., Kerr, I.D., and Callaghan, R. (2006):Br. J. Pharmacol.,149, 506–515.

    Article  CAS  PubMed  Google Scholar 

  6. Diah, S. K., Smitherman, P. K., Aldridge, J., Volk, E. L., Schneider, E., Townsend, A. J., and Morrow, C. S. (2001):Cancer Res,61, 5461–5467.

    CAS  PubMed  Google Scholar 

  7. Dietrich, C. G., de Waart, D. R., Ottenhoff, R., Bootsma, A. H., van Gennip, A. H., and Elferink, R. P. (2001):Carcinogenesis,22, 805–811.

    Article  CAS  PubMed  Google Scholar 

  8. Dietrich, C. G., de Waart, D. R., Ottenhoff, R., Schoots, I. G., and Elferink, R. P. (2001):Mol. Pharmacol.,59, 974–980.

    CAS  PubMed  Google Scholar 

  9. Dietrich, C. G., Ottenhoff, R., de Waart, D. R., and Oude Elferink, R. P. (2001):Toxicology,167, 73–81.

    Article  CAS  PubMed  Google Scholar 

  10. Dijkstra, M., Havinga, R., Vonk, R. J., and Kuipers, F. (1996):Life Sci.,59, 1237–1246.

    Article  CAS  PubMed  Google Scholar 

  11. Dubin, I. N. and Johnson, F. B. (1954):Medicine (Baltimore),33, 155–197.

    CAS  Google Scholar 

  12. Evers, R., de, H. M., Sparidans, R., Beijnen, J., Wielinga, P. R., Lankelma J., and Borst, P. (2000):Br. J. Cancer,83, 375–383.

    Article  CAS  PubMed  Google Scholar 

  13. Felton, J. S., Knize, M. G., Shen, N. H., Lewis, P. R., Andresen, B. D., Happe, J., and Hatch, F. T. (1986):Carcinogenesis,7, 1081–1086.

    Article  CAS  PubMed  Google Scholar 

  14. Fickert, P., Zollner, G., Fuchsbichler, A., Stumptner, C., Pojer, C., Zenz, R., Lammert, F., Stieger, B., Meier, P. J., Zatloukal, K., Denk, H., and Trauner, M. (2001):Gastroenterology,121, 170–183.

    Article  CAS  PubMed  Google Scholar 

  15. Guo, G. L., Lambert, G., Negishi, M., Ward, J. M., Brewer, H. B., Jr., Kliewer, S. A., González, F. J., and Sinal, C. J. (2003):J. Biol. Chem.,278, 45062–45071.

    Article  CAS  PubMed  Google Scholar 

  16. Honjo, Y., Morisaki, K., Huff, L. M., Robey, R. W., Hung, J., Dean, M., and Bates, S. E. (2002):Cancer Biol. Ther.,1, 696–702.

    CAS  PubMed  Google Scholar 

  17. Houwen, R., Dijkstra, M., Kuipers, F., Smit, E. P., Havinga, R., and Vonk, R. J. (1990):Biochem. Pharmacol.,39, 1039–1044.

    Article  CAS  PubMed  Google Scholar 

  18. Huang, L., Hoffman, T., and Vore, M. (1998):Hepatology,28, 1371–1377.

    Article  CAS  PubMed  Google Scholar 

  19. Jigorel, e., Le, V. M., Boursier-Neyret, C., Parmentier, Y., and Fardel, O. (2006):Drug Metab. Dispos.,34, 1756–1763.

    Article  CAS  PubMed  Google Scholar 

  20. Johnson, D. R. and Klaassen, C. D. (2002):Toxicol. Sci.,67, 182–189.

    Article  CAS  PubMed  Google Scholar 

  21. Jonker, J. W., Buitelaar, M., Wagenaar, E., Van der Valk, M. A., Scheffer, G. L., Scheper, R. J., Plosch, T., Kuipers, F., Elferink, R. P., Rosing, H., Beijnen, J. H., and Schinkel, A. H. (2002):Proc. Natl. Acad. Sci. U. S. A.,99, 15649–15654.

    Article  CAS  PubMed  Google Scholar 

  22. Kala, S. V., Kala, G., Prater, C. I., Sartorelli, A. C., and Lieberman, M. W. (2004):Chem. Res. Toxicol.,17, 243–249.

    Article  CAS  PubMed  Google Scholar 

  23. Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., Tontonoz, P., Kliewer, S., Willson, T. M., and Edwards, P. A. (2002):J. Biol. Chem.,277, 2908–2915.

    Article  CAS  PubMed  Google Scholar 

  24. Kauffmann, H. M., Pfannschmidt, S., Zoller, H., Benz, A., Vorderstemann, B., Webster,J. I. and Schrenk, D. (2002):Toxicology,171, 137–146.

    Article  CAS  PubMed  Google Scholar 

  25. Loo, T. W. and Clarke, D. M. (2001):J. Biol. Chem.,276, 36877–36880.

    Article  CAS  PubMed  Google Scholar 

  26. Loo, T. W. and Clarke, D. M. (2002):J. Biol. Chem.,277, 44332–44338.

    Article  CAS  PubMed  Google Scholar 

  27. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2003):J. Biol. Chem.,278, 39706–39710.

    Article  CAS  PubMed  Google Scholar 

  28. Lugo, M. R. and Sharom, F. J. (2005):Biochemistry,44, 643–655.

    Article  CAS  PubMed  Google Scholar 

  29. Martin, C., Berridge, G., Higgins, C. F., Mistry, P., Charlton, P., and Callaghan, R. (2000):Mol. Pharmacol. 58, 624–632.

    CAS  PubMed  Google Scholar 

  30. Mitomo, H., Kato, R., Ito, A., Kasamatsu, S., Ikegami, Y., Kii, I., Kudo, A., Kobatake, E., Sumino, Y., and Ishikawa, T. (2003):Biochem. J.,373, 767–774.

    Article  CAS  PubMed  Google Scholar 

  31. Owen, A., Chandler, B., Back, D. J., and Khoo, S. H. (2004):Antivir. Ther.,9, 819–821.

    CAS  PubMed  Google Scholar 

  32. Paulusma, C. C., Kool, M., Bosma, P. J., Scheffer, G. L., ter Borg, F., Scheper, R. J., Tytgat, G. N., Borst, P., Baas, F., and Oude Elferink, R. P. (1997):Hepatology,25, 1539–42.

    Article  CAS  PubMed  Google Scholar 

  33. Sakaeda, T. (2005):Drug. Metab. Pharmacokinet.,20, 391–414.

    Article  CAS  PubMed  Google Scholar 

  34. Schrenk, D., Baus, P. R., Ermel, N., Klein, C., Vorderstemann, B., and Kauffmann, H. M. (2001):Toxicol. Lett.,120, 51–57.

    Article  CAS  PubMed  Google Scholar 

  35. Shapiro, A. B., Fox, K., Lam, P., and Ling, V. (1999):Eur. J. Biochem.,259, 841–850.

    Article  CAS  PubMed  Google Scholar 

  36. Tzameli, I., Pissios, P., Schuetz, E. G., and Moore, D. D. (2000):Mol. Cell Biol.,20, 2951–2958.

    Article  CAS  PubMed  Google Scholar 

  37. Van Herwaarden, A. E., Jonker, J. W., Wagenaar, E., Brinkhuis, R. F., Schellens, J. H., Beijnen, J. H., and Schinkel, A. H. (2003):Cancer Res.,63, 6447–6452.

    PubMed  Google Scholar 

  38. Watkins, R. E., Maglich, J. M., Moore, L. B., Wisely, G. B., Noble, S. M., vis-Searles, P. R., Lambert, M. H., Kliewer, S. A., and Redinbo, M. R. (2003):Biochemistry,42, 1430–1438.

    Article  CAS  PubMed  Google Scholar 

  39. Xu, C., Li, C. Y., and Kong, A. N. (2005):Arch. Pharm. Res.,28, 249–268.

    Article  CAS  PubMed  Google Scholar 

  40. Yates, C. R., Zhang, W., Song, P., Li, S., Gaber, A. O., Kotb, M., Honaker, M. R., Alloway, R. R., and Meibohm, B. (2003):J. Clin. Pharmacol.,43, 555–564.

    CAS  PubMed  Google Scholar 

  41. Zelcer, N., Huisman, M. T., Reid, G., Wielinga, P., Breedveld, P., Kuil, A., Knipscheer, P., Schellens, J. H., Schinkel, A. H., and Borst, P. (2003):J. Biol. Chem.,278, 23538–23544.

    Article  CAS  PubMed  Google Scholar 

  42. Zelcer, N., van de, W. K., de, W. R., Scheffer, G. L., Marschall, H. U., Wielinga, P. R., Kuil, A., Kunne, C., Smith, A., van D., V, Wijnholds, J., Elferink, R. O., and Borst, P. (2006):J. Hepatol.,44, 768–775.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. AMC Liver Center, Academic Medical Center S1-162, Meibergdreef 69-71, 1105BK, Amsterdam, The Netherlands

    R. P. J. Oude Elferink & R. de Waart

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  1. R. P. J. Oude Elferink
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  2. R. de Waart
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Correspondence to R. P. J. Oude Elferink.

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Oude Elferink, R.P.J., de Waart, R. Transporters in the intestine limiting drug and toxin absorption. J Physiol Biochem 63, 75–81 (2007). https://doi.org/10.1007/BF03174087

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  • DOI: https://doi.org/10.1007/BF03174087

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