Geny M M Groothuis

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Animal models are commonly used in the preclinical development of new drugs to predict the metabolic behaviour of new compounds in humans. It is, however, important to realise that humans differ from animals with regards to isoform composition, expression and catalytic activities of drug-metabolising enzymes. In this review the authors describe similarities(More)
This review brings you up-to-date with the hepatocyte research on: 1) in vitro-in vivo correlations of metabolism and clearance; 2) CYP enzyme induction, regulation, and cross-talk using human hepatocytes and hepatocyte-like cell lines; 3) the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance; 4)(More)
Endotoxin-induced cholestasis in rodents is caused by hepatic downregulation of transporters, including the basolateral Na+-dependent taurocholate transporter (ntcp) and the canalicular bile salt export pump (bsep) and multidrug resistance-associated protein 2 (mrp2). Details about the regulation of the human transporter proteins during this process are(More)
Although the liver has long been thought to play the major role in drug metabolism, also the metabolic capacity of the intestine is more and more recognized. In vivo studies eventually pointed out not only the significance of first-pass metabolism by the intestinal wall for the bioavailability of several compounds, but also the relevance of transporters in(More)
The hallmark of liver fibrosis is an increased extracellular matrix deposition, caused by an activation of hepatic stellate cells (HSC). Therefore, this cell type is an important target for pharmacotherapeutic intervention. Antifibrotic drugs are not efficiently taken up by HSC or may produce unwanted side-effects outside the liver. Cell-specific delivery(More)
OBJECTIVES Procalcitonin (PCT) is a 13 kD protein of which plasma concentrations are strongly increased in inflammatory states. PCT concentrations are claimed to have a more powerful discriminatory value for bacterial infection than the acute phase proteins serum amyloid A (SAA) or C-reactive protein (CRP). The source of production and its mechanism of(More)
Precision-cut tissue slices (PCTS) are viable ex vivo explants of tissue with a reproducible, well defined thickness. They represent a mini-model of the organ under study and contain all cells of the tissue in their natural environment, leaving intercellular and cell-matrix interactions intact, and are therefore highly appropriate for studying multicellular(More)
Previous inhibition studies with taurocholate and cardiac glycosides suggested the presence of separate uptake systems for small "type I" (system1) and for bulky "type II" (system2) organic cations in rat hepatocytes. To identify the transport systems involved in type I and type II organic cation uptake, we compared the organic cation transport properties(More)
Precision-cut liver slices are presently used for various research objects, e.g. to study metabolism, transport, and toxicity of xenobiotics. Various incubation systems are presently employed, but a systematic comparison between these incubation systems with respect to preservation of slice function has not been performed yet. Therefore, we started a(More)
1. Organ-specific biotransformation was studied in human and rat liver, lung, kidney and small intestine slices and compared on a protein basis, using four model substances. 2. Deethylation of lidocaine was highest in liver slices from both man and rat, followed by the small intestine. 3. Metabolism of testosterone was highest in liver slices, but a(More)