Comparative study of the biotransformation of bepridil analogs in isolated liver cells from one rat. Relationships between structure and in vitro liver toxicity

  title={Comparative study of the biotransformation of bepridil analogs in isolated liver cells from one rat. Relationships between structure and in vitro liver toxicity},
  author={Elisabeth Damatte and M. -J. Galmier and C. Lartigue-Mattei and J. F. Pognat and Norbert Busch and Jean Louis Chabard},
  journal={European Journal of Drug Metabolism and Pharmacokinetics},
SummaryThe biotransformation of several analogs of the anti-calcium agent bepridil was studied comparatively in liver cells isolated from one rat. Three types of metabolites were identified by mass spectrometry, resulting from three phase I reactions: hydroxylation, N-debenzylation and pyrrolidine ring opening. The amount of each bepridil analog untransformed after 18 h of incubation depended on its liver toxicity rather than on its concentration in the culture medium. The proportion of phase I… 
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Metabolism of bepridil in laboratory animals and humans.
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Activities of cytosolic and microsomal drug oxidases of rat hepatocytes in primary culture.
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  • Biology, Medicine
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  • 1989
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The metabolism of drugs in isolated hepatocytes correlates with in vivo drug metabolism better than does metabolism in the hepatic 9000g supernatant fraction or microsomes.
Human hepatocyte cultures: a model of pharmaco-toxicological studies.
Human hepatocytes, particularly when mixed with rat-liver epithelial cells, may provide a valuable tool for predicting the metabolic pathways and hepatotoxicity of new drugs in man.
Primary cultures and the levels of cytochromeP450 in hepatocytes from mouse, rat, hamster, and rabbit liver
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