foto

Dr. D.R. de Waart

Position
Other
Main activities
Research
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 CC, Dewaart DR, Kunne C, Mok KS, Oude Elferink RPJ, Activity of the Bile Salt Export Pump (ABCB11) Is Critically Dependent on Canalicular Membrane Cholesterol Content. J BIOL CHEM 2009;284 (15):9947-9954 [PubMed]
  • Manautou JE, de Waart DR, Kunne C, Zelcer N, Goedken M, Borst P, Elferink RO, Altered disposition of acetaminophen in mice with a disruption of the Mrp3 gene. HEPATOLOGY 2005;42 (5):1091-1098 [PubMed]
  • de Waart DR, Hausler S, Vlaming ML, Kunne C, Hanggi E, Gruss HJ, Oude Elferink RPJ, Stieger B, Hepatic Transport Mechanisms of Cholyl-L-Lysyl-Fluorescein. J PHARMACOL EXP THER 2010;334 (1):78-86 [PubMed]
  • de Waart DR, Vlaming MLH, Kunne C, Schinkel AH, Oude Elferink RPJ, Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. DRUG METAB DISPOS 2009;37 (8):1698-1702 [PubMed]
  • Dietrich CG, de Waart DR, Ottenhoff R, Bootsma AH, van Gennip AH, Elferink RP, 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. dr. R.P.J. Oude Elferink PhD (Hepatic metabolism and transport processes)