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RECORD NUMBER: 22 OF 69

OLS Field Name OLS Field Data
Main Title Evaluation of Octamethylcyclotetrasiloxane (D4) as a Potential Inhibitor of Human Cytochrome P450 Enzymes, with Cover Letter dated 12/01/1998.
CORP Author Dow Corning Corp., Midland, MI.; Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
Year Published 1998
Stock Number OTS0573867
Additional Subjects Toxicology ; Health effects ; Octamethylcyclotetrasiloxane ; Pharmaco kinetics ; Mammals ; Humans ; In vitro ; CAS No 541-02-6 ; CAS No 541-05-9 ; CAS No 556-67-2
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NTIS  OTS0573867 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. 09/09/2010
Collation 130p
Abstract
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.