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Metabolism human hepatocyte

Easterbrook, J., Liu, C., Sakai, Y. and Li, A.P. (2001) Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 29, 141-144. [Pg.224]

Ponsoda, X., Donato, M.T., Perez-Cataldo, G., Gomez-Lechon, M.J. and Castell, J.V. (2004) Drug metabolism by cultured human hepatocytes how far are we from the in vivo reality Alternatives to Laboratory Animals, 32 (2), 101—110. [Pg.239]

McGinnity, D.F., Berry, A.J., Kenny J.R., Grime, K. and Riley, R.J. (2006) Evaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes. Drug Metabolism and Disposition, 34 (8), 1291-1300. [Pg.244]

Primary hepatocytes are a common in vitro system to evaluate metabolism, toxicity and enzyme induction [67-69]. Human hepatocytes are considered the most relevant system to evaluate or predict human metabolism or effects of a new dmg. A significant... [Pg.304]

Mills, J.B., Rose, K.A., Sadagopan, N., Sahi, J. and de Morais, S.M. (2004) Induction of drug metabolism enzymes and MDR1 using a novel human hepatocyte cell line. The Journal of Pharmacology and Experimented Therapeutics, 309, 303-309. [Pg.315]

D. K. Monteith, S. C. Storm, A Comparison of the Inhibition of Deacetylase in Primary Cultures of Rat and Human Hepatocytes Effecting Metabolism and DNA-Binding of 2-Acetylaminofluorene , Cell Biol. Toxicol. 1990, 6, 269-284. [Pg.175]

The first studies with isolated human hepatocytes concentrated on the characterization of these hepatocytes, as well as on the improvement of the isolation procedure, and the possibilities of culturing these cells [16,19-24]. Thereafter studies were performed to investigate the metabolism of drugs [25-28], in which emphasis was often put on the activity and concentration of cytochrome P450 isoforms. Nowadays, hepatocytes are more generally used in metabolic studies of specific compounds, in order to unravel potential species differences and... [Pg.310]

Sandker GW, Isolated human hepatocytes a research tool for investigations on drug transport, drug metabolism and liver transplantation. PhD thesis. University of Groningen, 1993. [Pg.328]

B[/ ]P metabolites have been shown to bind to DNA in culmred human hepatocytes and in human bladder and tracheobronchial explants. The metabolites identified were identical to those produced in other species and differed only in the relative percentages of formation. Human tissues were most active in metabolizing P>[a P and exhibited at least a threefold higher covalent binding of metabolites to DNA than hamsters, dogs, monkeys, or rats. In addition, P>[a P has been tested extensively in several bacterial and mammalian cell systems and has been chosen as a positive control for the validation of some of these systems. ... [Pg.77]

Monteith DK, Novoting A, Michalopoulos G, Stron SC Metabolism of benzo[ ]pyrene in primary cultures of human hepatocytes Dose-response over a four-log range. Carcinogenesis 8 983-988, 1987... [Pg.77]

SRI evaluates drug metabolism and drug interactions, using human and animal (rat, dog, and monkey) tissue models based on human hepatocytes. It also extends services for the metabolite profiling of drug candidates using hepa-... [Pg.495]

Hariparsad, N., Carr, B.A., Evers, R. and Chu, X. (2008) Comparison of immortalized Ea2N-4 cells and human hepatocytes as in vitro models for cytochrome P450 induction. Drug Metabolism and Disposition The Biological Fate of Chemicals, 36, 1046-1055. [Pg.194]

Ripp, S.L., Mills, J.B., Eahmi, O.A., Trevena, K.A., Liras, J.L., Maurer, T.S. and de Morals, S.M. (2006) Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused hy CYP3A4 induction. Drug Metabolism and Disposition The Biological Fate of Chemicals, 34, 1742—1748. [Pg.194]

Using human physiology and in vitro data and clinically relevant input parameters (i.e., metabolic stability in human hepatocytes and microsomes as well as prothrombin time measured in various batches of human plasma) the model was extended to human. This human PK/PD model was then used to investigate the impact of the various physicochemical, pharmacokinetic and pharmacodynamic properties on the anticoagulant profile (i.e., prothrombin time) expected in man. [Pg.229]

In a first step the scaling of intrinsic clearances determined in rat hepatocytes was compared to in vivo clearance. When taking account of non-linearity, the estimated hepatic metabolic clearance values were in reasonable agreement with observed total clearances, which ranged from 7 to 35 mL/min/kg, and it was considered reasonable to estimate the expected clearances in human by a similar scaling of human hepatocyte data. The error around the mean predicted human clearance was based on the variability seen in different batches of human hepatocytes. [Pg.235]

Metabolic competence of HepG2 human hepatoblastoma cells depends on the source and culture conditions. They have both Phase I and II metabolizing enzymes. Cytochrome P450 enzymes are found in much lower levels in HepG2 cells than in primary human hepatocytes but many of these enzymes are inducible, including CYPlAl, 1A2, 2B6, 2E1 and 3A4. The latter metabolizes approximately 50% of drugs currently on the market [32]. [Pg.340]

The effect of botanical products on the expression of drug-metabolizing enzymes or transport proteins can be examined in cell culture with established cell lines or primary human hepatocytes. The cells are incubated under... [Pg.62]

Dichloromethane induced DNA-protein cross-links in vitro in hepatocytes of male B6C3Fi mice but not in hepatocytes of Fischer 344 rats, Syrian hamsters or in human hepatocytes with functional GSTTl genes. DNA-protein cross-links were also induced in Chinese hamster ovary CHO cells exposed to dichloromethane with or without exogenous metabolic activation. DNA damage was greater, however, in the presence of metabolic activation. [Pg.284]

Human liver preparations metabolize ethylene dibromide to water-soluble and irreversibly protein- and DNA-bound metabolites by both cytochrome P450 and glutathione S-transferase (GST) enzymes (Wiersma et al., 1986). DNA adduct formation occurs also in isolated human hepatocytes (Cmarik et al., 1990). [Pg.646]

Pre-clinical studies resulted in the development of a robust route of synthesis for CF101 in a large scale production. The active pharmaceutical ingredient was found to be highly stable for a long period of time. CF101 was slowly metabolized in mouse, rat, rabbit, monkey and human hepatocytes and studies with human hepatic... [Pg.294]


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See also in sourсe #XX -- [ Pg.234 ]




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