Enzyme metabolic activation

Drug interactions No drug interaction studies have been conducted with Avonex. Other interferons have been found to reduce cytochrome P-450-mediated drug metabolism. Hepatic microsomes isolated from Avonex-treated rhesus monkeys showed no influence on hepatic P-450 enzyme metabolism activity. 

In the assessment of placental toxicology of any foreign chemical substances, there are two major areas of concern what the placenta does to xenobiotics and what xenobiotics do to the placenta (Myllynen et ai, 2005). In the former area the major topics of concern are the entry and possible storage of substances in placental cells and through the placenta, aided perhaps by various transporters and efflux pumps the distribution and binding of compounds in placental cells and biotransformafion of substances by intracellular enzymes. Metabolic activation and production of reactive intermediates by placental enzymes link these areas with toxicodynamics of placental toxicants. In the latter area, effects of compounds on placental blood flow and vasculature and the presence of membrane and intracellular receptors, enzymes, and other potential targets for foreign substances are important areas of inquiry for placental toxicity. 

Fu PP, Xia Q, Lin G (2004) Pyrrolizidine alkaloids - genotoxicity, metabolism enzymes, metabolic activation, and mechanism. Drug Metab Revs 36 1-55... 

The interactions may be physicochemical without the participation of biological mechanisms for example, deep lung exposure to highly soluble irritative gases, such as sulfur dioxide, may become enhanced due to adsorption of the gas onto fine particles. Biological interactions may occur at all stages and body sites. For example, toxicity is increased when adverse effects are due to some reactive metabolic intermediate and exposure to another agent stimulates its metabolic activation (enzyme induction). 

A prodrag is a drug that is not by itself pharmacologically active but needs metabolic activation by an enzyme. Examples are the cytostatic cyclophosphamide, which is activated by hydroxylation catalyzed by CYP2B6, or HMGCoA reductase inhibitor, lovastatin, which contains... 

Various factors affect the activities of the enzymes metabolizing xenobiotics. The activities of these enzymes may differ substantially among species. Thus, for example, the possible toxicity or carcinogenicity of xenobiotics cannot be extrapolated freely from one species to another. There are significant differences in enzyme activities among individuals, many of which appear to be due to genetic factors. The activities of some of these enzymes vary according to age and sex. 

To date, there is very little known about if and how phytochemicals modulate the metabolism of GIT tissues other than the liver. Of particular interest are the xenobiotic metabolizing enzymes of the GIT, which are involved with transformation of drugs and toxins. Whereas the metabolic activities of the resident microflora dominate in the large intestine, mucosal enzyme activities are more important in the small intestine where bacterial densities are lower and the villi and microvilli increase the area of exposure. 

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