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(2000)
The MEIC in vitro Database
S. Halwachs, C. Kneuer, W. Honscha (2005)
Endogenous expression of liver-specific drug transporters for organic anions in the rat hepatocytoma fusion cell line HPCT-1E3.European journal of cell biology, 84 7
B. Hagenbuch, P. Meier (2004)
Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional propertiesPflügers Archiv, 447
B. Ekwall (1999)
Overview of the Final MEIC Results: II. The In Vitro--In Vivo Evaluation, Including the Selection of a Practical Battery of Cell Tests for Prediction of Acute Lethal Blood Concentrations in Humans.Toxicology in vitro : an international journal published in association with BIBRA, 13 4-5
J. Cervenak, H. Andrikovics, C. Ozvegy-Laczka, A. Tordai, K. Német, A. Váradi, B. Sarkadi (2006)
The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology.Cancer letters, 234 1
W. Löscher, H. Potschka (2005)
Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseasesProgress in Neurobiology, 76
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CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells.Drug metabolism and disposition: the biological fate of chemicals, 24 3
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H. Kaddouri, Serge Nakache, S. Houzé, F. Mentré, J. bras (2006)
Assessment of the Drug Susceptibility of Plasmodium falciparum Clinical Isolates from Africa by Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-Percent Inhibitory ConcentrationAntimicrobial Agents and Chemotherapy, 50
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Terfenadine (Seldane): a new drug for restoring sensitivity to multidrug resistant cancer cells.Biochemical pharmacology, 45 2
Ernst Petzinger, W. Follmann, M. Blumrich, Paul Walther, J. Hentschel, P. Bette, M. Maurice, G. Feldmann (1994)
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W. Halle, M. Halder, Andrew Worth, E. Genschow (2003)
The Registry of Cytotoxicity: Toxicity Testing in Cell Cultures to Predict Acute Toxicity (LD50) and to Reduce Testing in Animals 1Alternatives to Laboratory Animals, 31
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P. Dierickx (2000)
Cytotoxicity of the MEIC reference chemicals in rat hepatoma-derived Fa32 cells.Toxicology, 150 1-3
Y. Kato, H. Suzuki, Y. Sugiyama (2002)
Toxicological implications of hepatobiliary transporters.Toxicology, 181-182
Bjoern Peters, H. Holzhütter (2002)
In Vitro Phototoxicity Testing: Development and Validation of a New Concentration Response Analysis Software and Biostatistical Analyses Related to the Use of Various Prediction ModelsAlternatives to Laboratory Animals, 30
D. Sweet (2005)
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K. Faber, Michael Müller, P. Jansen (2003)
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P. Dierickx (2005)
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I. Bondesson, B. Ekwall, S. Hellberg, L. Romert, K. Stenberg, E. Walum (1989)
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A battery of in vitro methods has been developed for the prediction of acute oral toxicity, to reduce the number of animals used for this purpose. However, the results of these tests correlate more closely with lethal serum concentrations than with lethal doses. To address this issue, we have further evaluated the HPCT-1E3 model, which may be better able to emulate toxicokinetic factors that occur in vivo, due to the presence in these hepatocytoma cells of endogenous transmembrane carriers and a basal activity of xenobiotic metabolism. IC50 values produced by using the MTT test after a 48-hour incubation with 20 randomly-selected MEIC substances, correlated better with human oral LD50 values than with LC50 data, supporting this hypothesis. As with other models, the toxicity of receptor-specific rather than cytotoxic substances, for example digoxin, was underpredicted. When digoxin was removed from the correlation analysis, the coefficient of determination (r2) improved to 0.81, and none of remaining chemicals were wrongly predicted by more than one order of magnitude. IC50 values obtained with HepG2 cells under similar conditions (MEIC Test No. 3, 24 hours, MTT) correlated with human LD50 data with a r2 value of 0.55. A direct comparison of HPCT-1E3 and HepG2 cells further suggested that the differences between them may be due to transport processes. In conclusion, the HPCT-1E3 model may be valuable in improving the prediction of lethal doses, rather than lethal serum concentrations.
Alternatives to Laboratory Animals – SAGE
Published: Aug 1, 2007
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