||Evaluation of Octamethylcyclotetrasiloxane (D4) as a Potential Inhibitor of Human Cytochrome P450 Enzymes, with Cover Letter dated 12/01/1998.
||Dow Corning Corp., Midland, MI.; Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
Health effects ;
Pharmaco kinetics ;
In vitro ;
CAS No 541-02-6 ;
CAS No 541-05-9 ;
CAS No 556-67-2
||Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy.
||The duration and/or intensity of action of numerous drugs and other xenobiotics is determined by their rate of metabolism (biotransformation) by several cytochrome P450 enzymes that are localized primarily in liver endopiasmic reticulum (microsomes). If a compound is metabolized by a particular P450 enzyme, it will competitively inhibit the metabolism of other drugs metabolized by the same enzyme and, conversely, these same drugs will competitively inhibit the metabolism of that compound. The degree of inhibition will be determined by the concentrations of the given compound and of other drugs and their affinity (Km and Ki) for binding to the P450 enzyme that metabolizes them. Alternatively, compounds can be activated by P450 enzymes to metabolites that can reversibly or irreversibly inhibit P450 enzymes. This type of inhibitor most often exhibits kinetics characteristic of non-competitive inhibitors, although mixed inhibition (competitive and non-competitive) is also possible. The inhibitory potential of metabolism-dependent inhibitors will depend on the rate of inactivation of the P450 enzyme, the dose of inhibitor administered and the total content of the P450 enzyme in the liver.
||The quality of the documents listed in the Office of Toxic Substances database may not meet usual NTIS standards but are included to further the opportunity for the scientific and technical community to locate materials which may not be available elsewhere. The content is the responsibility of OTS. Sponsored by Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
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|PUB Date Free Form
||7 Dec 1998
||57Y; 57U; 68G; 99; 44G
||PC A08/MF A08