cytochrome P-450 system

cytochrome P-450 system

a heterogeneous group of enzymes that catalyzes various oxidative reactions in the human liver, intestine, kidney, lung, and central nervous system. These enzymes are involved in the metabolism of many endogenous and exogenous substrates, including drugs, toxins, hormones, and natural plant products. Cytochrome P-450 enzymes are classified on the basis of chemical structure (amino acid sequencing). The designation of each enzyme is CYP followed by a numeral for the family to which it has been assigned, a letter for its subfamily, and sometimes a second numeral for the individual enzyme.

The steady increase in the number and variety of pharmaceutical agents available for the treatment of infections, degenerative and malignant conditions, mental disorders, and other diseases has led to polypharmacy, with attendant risks of undesirable drug interactions. Disturbances in the function of the cytochrome P-450 system are increasingly recognized as important causes of such interactions. When a drug increases the formation of a P-450 enzyme, other drugs metabolized by that enzyme are eliminated more rapidly and may fail to produce the desired therapeutic effects. In contrast, a drug that inhibits P-450 enzyme activity can retard the metabolism of substrate drugs, with resultant increases in serum and tissue levels and in drug effects, including side-effects. Inhibition usually involves competition between drugs for the same binding site on an enzyme molecule. Reversible inhibition is the most common mechanism of drug interactions involving the P-450 system. In general, drugs compete for a specific P-450 isoenzyme. Examples of agents that cause interactions through reversible inhibition are fluoroquinolone antibiotics, cimetidine, ketoconazole, and protease inhibitors used in the treatment of AIDS. The most abundant human cytochrome P-450 enzyme is CYP3A4, which is involved in the metabolism of about 50% of medicines in current use. Ethnic differences in the expression of CYP2D6 explain why whites are more likely than blacks and Asians to experience toxicity from accumulation and excessive serum levels of drugs metabolized by this enzyme, such as tricyclic antidepressants, SSRIs, antipsychotics, and beta-blockers.

cy·to·chrome P-450 sys·tem

(CYP) (sī'tō-krōm sis'tĕm)
A heterogeneous group of enzymes that catalyze various oxidative reactions in the human liver, intestine, kidney, lung, and central nervous system; these enzymes are involved in the metabolism of many endogenous and exogenous substrates, including drugs, toxins, hormones, and natural plant products. Cytochrome P-450 enzymes are classified on the basis of chemical structure (amino acid sequencing). The designation of each enzyme is CYP followed by a numeral for the family to which it has been assigned, a letter for its subfamily, and sometimes a second numeral for the individual enzyme.

cy·to·chrome P-450 sys·tem

(sī'tō-krōm sis'tĕm)
A heterogeneous group of enzymes that catalyzes various oxidative reactions in the human liver, intestines, kidneys, lungs, and central nervous system.
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References in periodicals archive ?
Clopidogrel is a prodrug that requires activation by the hepatic cytochrome P-450 system to become an active metabolite [3].
1987) Hydroxylation of fatty acids and alcohols by hepatic microsomal cytochrome P-450 system from the Mongolian gerbil.
As ethnic variations in the Cytochrome P-450 system continue to be discovered and better understood, it is increasingly important that individual genetic variations be considered when medications are prescribed (Lin, Smith, & Ortiz, 2001; Munoz & Hilgenberg, 2005).
Two key types of pharmacokinetic interactions to remember are those that prolong the QT interval and those that interfere with the cytochrome P-450 system (CYP).
Through the cytochrome P-450 system, many antiretroviral agents interact with opioids, including methadone (see box), levomethadyl acetate (LAAM), and buprenorphine.
All 55 participants smoked at baseline, and constituents of cigarette smoke activate the same cytochrome P-450 system enzyme that metabolizes olanzapine (Zyprexa), haloperidol decanoate (Haldol), and fluphenazine decanoate.
In mammals and other vertebrates the cytochrome P-450 system is used to oxidize a wide range of endogenous and exogenous compounds including fatty acids, steroids, drugs and pollutants (Geng et al.
Use with caution or lower dosages for ptients with renal or hepatic impairment or in conjunction with other drugs acting on the cytochrome P-450 system.
Highlighted drug interactions, particularly among drugs metabolized by the cytochrome P-450 system.
Also several medications are known to induce the cytochrome P-450 system, which will increase the rate of MEGX production [21,22].

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