Contribution of the murine mdr1a P-glycoprotein to hepatobiliary and intestinal elimination of cationic drugs as measured in mice with an mdr1a gene disruption

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
J W SmitD K Meijer

Abstract

In the mouse, both the mdr1a and the mdr1b gene encode drug-transporting P-glycoproteins. The mdr1a P-glycoprotein is expressed in epithelial cells of, among others, the liver and the intestine. Furthermore, the mdr1b gene product is found in the liver but is not detectable in the intestine. To establish the potential involvement of P-glycoprotein in the elimination of cationic amphiphilic drugs from the body, we investigated biliary, intestinal, and urinary excretion in mice with a homozygous disruption of the mdr1a gene (mdr1a(-/-) mice). These mice are fully viable under laboratory conditions and have normal bile flow. Cumulative biliary excretion (expressed as percent of the intravenously administered dose excreted over a 1-hour period) of several cationic compounds was decreased as follows in mdr1a(-/-) mice compared with the wild-type animals: tri-n-butylmethylammonium (TBuMA), 0.7% versus 2.1%; azidoprocainamide methoiodide (APM), 3.8% versus 7.6%; and vecuronium, 22.7% versus 41.3%. The luminal secretion of both TBuMA and APM in the small intestine was profoundly decreased, respectively 4.6-fold (1.8% vs. 8.2% in the wild-type) and 7.9-fold (1.6% vs. 10.3% in the wild-type) in mdr1a(-/-) mice. Thus mdr1a P-glycoprotein ...Continue Reading

References

Jan 15, 1977·Biochemical Pharmacology·K Turnheim, F O Lauterbach
Nov 11, 1976·Biochimica Et Biophysica Acta·R L Juliano, V Ling
Jan 1, 1992·Annual Review of Cell Biology·C F Higgins
Jan 1, 1992·Annual Review of Physiology·J L BoyerP J Meier
Jul 27, 1992·Biochimica Et Biophysica Acta·M TakanoR Hori
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F ThiebautM C Willingham
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C Cordon-CardoJ R Bertino
Aug 1, 1983·Experimental and Clinical Endocrinology·W HublB Neef
Jun 1, 1983·Pflügers Archiv : European journal of physiology·K J de NeefJ R Jansen
Feb 1, 1995·Journal of Bioenergetics and Biomembranes·C F Higgins
Sep 8, 1995·Cell·C F Higgins
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·B L Leu, J D Huang
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Jan 1, 1994·Journal of Computer Assisted Tomography·R H WachsbergA Adekosan
Jul 17, 1996·Journal of the National Cancer Institute·J van AsperenO van Tellingen
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·A SparreboomO van Tellingen
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·A H SchinkelP Borst

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Citations

Jan 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J H HayesJ L Boyer
May 2, 2002·Molecular Reproduction and Development·Robert P EricksonRandall A Heidenreich
Jan 30, 2007·Cancer Metastasis Reviews·Sushma YadavSanjay Awasthi
Sep 25, 1999·European Journal of Pharmacology·F MartelI Azevedo
Jul 25, 2000·Developmental and Comparative Immunology·M D EisenbraunR A Miller
Nov 7, 1999·Journal of Hepatology·A J Smith, R P Oude Elferink
Jan 22, 2003·Advanced Drug Delivery Reviews·Yan ZhangDonald W Miller
Jan 22, 2003·Advanced Drug Delivery Reviews·Jiunn H Lin
Jun 6, 2000·Advanced Drug Delivery Reviews·A H Schinkel
Dec 21, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G J HooiveldM Müller
Apr 6, 2002·British Journal of Pharmacology·Guido J E J HooiveldMichael Müller
Mar 27, 2002·The Pharmacogenomics Journal·U Brinkmann, M Eichelbaum
Oct 17, 2006·Clinical Microbiology Reviews·Joseph MeletiadisThomas J Walsh
Feb 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin G Chen, Branimir I Sikic
Apr 2, 2005·Biological & Pharmaceutical Bulletin·Young-Joo LeeChang-Koo Shim
Jul 11, 2001·Pharmacotherapy·C J MathenyG M Pollack
Dec 20, 2002·Clinical Pharmacokinetics·Jiunn H Lin, Masayo Yamazaki
Jan 13, 2000·Biochemical and Biophysical Research Communications·T G Tessner, W F Stenson
Feb 25, 2009·Investigational New Drugs·J H BeumerO van Tellingen
Jun 12, 2009·Drug Metabolism Reviews·Lesley A StanleyC Roland Wolf
May 9, 2002·Drug Metabolism Reviews·Richard B Kim
Jul 18, 2008·Experimental Animals·Guohong ZhangMasayuki Mori
Nov 26, 2009·Chemistry & Biodiversity·Gregory J AngerMicheline Piquette-Miller
Dec 3, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Renxue WangVictor Ling
May 16, 2001·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·B MahmoodJ F Watchko
Feb 12, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yufei HeChangxiao Liu
Jan 25, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tsuyoshi MikkaichiTakashi Izumi
Jun 30, 2005·The Journal of Pharmacology and Experimental Therapeutics·Maria J MonteJose J G Marin
Mar 29, 2003·Physiological Reviews·Michael Trauner, James L Boyer
Nov 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·K Sandy Pang
Apr 16, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Joanna M LittleAnna Radominska-Pandya
Jan 8, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Kalitsky-SzirtesM Piquette-Miller

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