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Reactive drug metabolism

Hinson, J.A. Reid, A.B. McCullough, S.S. James, L.P. (2004). Acetaminophen-induced hepatotoxicity role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metabolism Reviews, Vol.36, No. 3-4, (January 2004), pp. 805-822, ISSN 0360-2532. [Pg.21]

The presence of chemically reactive structural features in potential drug candidates, especially when caused by metabolism, has been linked to idiosyncratic toxicity [56,57] although in most cases this is hard to prove unambiguously, and there is no evidence that idiosyncratic toxicity is correlated with specific physical properties per se. The best strategy for the medicinal chemist is avoidance of the liabilities associated with inherently chemically reactive or metabolically activated functional groups [58]. For reactive metabolites, protein covalent-binding screens [59] and genetic toxicity tests (Ames) of putative metabolites, for example, embedded anilines, can be employed in risky chemical series. [Pg.401]

E.I. Iwuoha, S. Joseph, Z. Zhang, M.R. Smyth, U. Fuhr, and P.R. Ortiz de Montellano, Drug metabolism biosensors electrochemical reactivities of cytochrome CYP101 immobilised in synthetic vesicular systems. J. Pharm. Biom. Anal. 17, 1101-1110 (1998). [Pg.602]

Schrag, M.L. and Wienkers, L.C. (2001) Triazolam substrate inhibition evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. Drug Metabolism and Disposition, 29 (1), 70-75. [Pg.237]

Fontana, E., Dansette, P.M. and Poli, S.M. (2005) Cytochrome P450 enzymes mechanism based inhibitors common sub-structures and reactivity. Current Drug Metabolism, 6, 413 -54. [Pg.290]

Hydrogen peroxide supports hepatocyte P450 catalysed xenobiotic/drug metabolic activation to form cytotoxic reactive intermediates. Adv Exp Med Biol 500 233-236. [Pg.82]

Ju, C. andUetrecht, J.P. (2002) Mechanism of idiosyncratic drug reactions reactive metabolites formation, protein binding and the regulation of the immune system. Current Drug Metabolism, 3, 367-377. [Pg.162]

Madsen, K.G. et al. (2007) Development and evaluation of an electrochemical method for studying reactive phase-I metabolites correlation to in vitro drug metabolism. Chemical Research in Toxicology, 20 (5), 821-831. [Pg.377]


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Drug Metabolism and Reactive Metabolites

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