Bioavailable toxicity identification

Fig. 6 Different steps to be followed in the new concept of a bioavailable toxicity identification evaluation (BTIE) method...

Identification of metabolic reactions at an early phase can significantly affect the drug discovery process, because bioavailability, activity, toxicity, distribution and final elimination all depend on metabolic biotransformations [1], Once obtained, this information can help researchers judge whether or not a potential candidate should be eliminated from the pipeline or modified to reduce the affinity for CYP antitarget enzymes. 

The real risks resulting from the bioavailability and mobility of pollutants to be determined 9.7.1 Identification of Toxic Compounds... 

Drug Discovery Today 7 25-27 Li AP (2004) In vitro approaches to evaluate ADMET drug properties. Curr Top Med Chem 4 701-706 Li W, Escarpe PA, Eisenberg EJ et al. (1998) Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrobial Agents and Chemotherapy 42 647-653 Los LE, Welsh DA, Herold EG et al. (1996) Gender differences in toxicokinetics, liver metabolism, and plasma esterase activity observations from a chronic (27-week) toxicity study of enalapril/diltiazem combinations in rats. Drug Metab Dispos 24 28-33... 

Complete information on pollution available. If all contaminants present in the sample have been analysed using conventional physical or chemical methods, the application of bioassays provides further information e.g. on toxicity interactions and bioavailability. It has to be emphasised that for multiple contamination, bioassays reveal an overall combined toxicity response to the bioavailable part of each contaminant present in the mixture. The identification of the bioavailable fraction of a particular substance by relating the measured effect to the measured concentration of the chemical is only possible for a single substance contamination (only one toxic chemical present). Although it may be tempting for risk assessors, the response of multiple pollution cannot be used to calculate the bioavailable fraction (percentage of the total concentration of a compound) of a particular chemical from the mixture, unless toxicant... 

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