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PhD D.R. de Waart

Position
Research Associate
Main activities
Research, Other
Specialisation
transport of drugs and compounds mediated by multidrug resistant associated proteins
Focus of research

The plasma membrane of hepatocytes harbors several drug extrusion pumps, such as MRP2 (ABCC2), ABCG2 and MDR1 (ABCB1) in the canalicular membrane and MRP3 (ABCC3) and MRP4 (ABCC4) in the basolateral membrane. These ATP-dependent transporters are expressed both in liver and in the intestine; therefore they determine to a large extent the pharmacokinetic behaviour of drugs. In mouse strains with disruptions of the various transporter genes (as well as combined gene disruptions) we determine the role of these transporters in pharmacokinetics of various classes of drugs. These issues will become increasingly important for drug development as well as the elucidation of drug-drug interactions.
 

Key publications
  • Paulusma Coen C., Dewaart D. Rudi, Kunne Cindy, Mok Kam S., Oude Elferink Ronald P. J. Activity of the Bile Salt Export Pump (ABCB11) Is Critically Dependent on Canalicular Membrane Cholesterol Content Journal of biological chemistry 2009;284 (15):9947-9954 [PubMed]
  • Manautou José E., de Waart Dirk R., Kunne Cindy, Zelcer Noam, Goedken Michael, Borst Piet, Elferink Ronald Oude Altered disposition of acetaminophen in mice with a disruption of the Mrp3 gene Hepatology (Baltimore, Md.) 2005;42 (5):1091-1098 [PubMed]
  • de Waart Dirk R., Hausler Stephanie, Vlaming Maria L., Kunne Cindy, Hanggi Emanuel, Gruss Hans-Jurgen, Oude Elferink R. P. J., Stieger Bruno Hepatic Transport Mechanisms of Cholyl-L-Lysyl-Fluorescein Journal of pharmacology and experimental therapeutics 2010;334 (1):78-86 [PubMed]
  • de Waart Dirk R., Vlaming Maria L. H., Kunne Cindy, Schinkel Alfred H., Oude Elferink Ronald P. J. Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2 Drug metabolism and disposition: the biological fate of chemicals 2009;37 (8):1698-1702 [PubMed]
  • Dietrich C. G., de Waart D. R., Ottenhoff R., Bootsma A. H., van Gennip A. H., Elferink R. P. Mrp2-deficiency in the rat impairs biliary and intestinal excretion and influences metabolism and disposition of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo Carcinogenesis 2001;22 (5):805-811 [PubMed]
All Publications
Research programmes

Prof. PhD R.P.J. Oude Elferink (Hepatic metabolism and transport processes)