CYP enzymes P450 cytochrome

Aripiprazole is hepatically metabolized, mainly by two cytochrome P450 enzymes CYP 2D6 and CYP 3A4. Therefore, dosage adjustments are necessary when this medication is given with other medications that either inhibit or induce these enzymes. For example, the dose of aripiprazole should be halved when this medication is given with ketoconazole, a CYP 3A4 inhibitor, or at least decreased when given with fluoxetine, a CYP 2D6 inhibitor. When aripiprazole is given with CYP 3A4 inducers such as carbamazepine, the dose should be doubled. 

The family of cytochrome P450 enzymes (CYPs) plays a central role in the metabolism of a tvide variety of xenobiotics including clinically important drugs. A number of approaches such as 3D-QSAR and pharmacophore modeling have been used to predict inhibitory potential and metabolism of drug candidates [40-45],... 

Oseltamivir phosphate and the carboxylate do not interact with the cytochrome P450 enzymes (CYPs) in vitro. Their protein binding is low. No clinically significant drug interactions have been recognized to date. Oseltamivir does not appear to impair fertility or to be teratogenic in animal... 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

The numerous biotransformations catalyzed by cytochrome P450 enzymes include aromatic and aliphatic hydroxylations, epoxidations of olefinic and aromatic structures, oxidations and oxidative dealkylations of heteroatoms and as well as some reductive reactions. Cytochromes P450 of higher animals may be classified into two broad categories depending on whether their substrates are primarily endogenous or xenobiotic substances. Thus, CYP enzymes of families 1-3 catalyze... 

The membrane-attached cytochrome P450 enzymes are involved in a significant fraction of events associated with drug metabolism. Most of the cytochrome P450 (CYP) catalyzed reactions lead to the detoxification of xenobiotics, by forming hydrophilic metabolites that can be readily excreted from the body. 

Galantamine is metabolized primarily by CYP 2D6 and 3A4, and levels may be altered by inducers or inhibitors of these enzymes. Galantamine has not been shown to inhibit major cytochrome P450 enzymes. However, the pharmacodynamic interactions associated with other cholinesterase inhibitors may occur. 

The first stage 1 reaction i.e. oxidation-reduction are generated by a common hydroxy-lating enzyme system (cytochrome P450 system CYP), which is located in... 

Whereas most, if not all, of the enzymes involved in xenobiotic metabolism can form reactive metabolites (Table 8.1), the enzyme systems most frequently involved in the activation of xenobiotics are those which catalyze oxidation reactions. The cytochrome P450 monooxygenases (CYP) are by far the most important enzymes involved in the oxidation of xenobiotics. This is because of the abundance of CYP (especially in the liver), the numerous isozymes of CYP, and the ability of CYP to be induced by xenobiotic compounds. 

Patients with hepatic insufficiency may not tolerate the drug at usual doses, however, because of increased area under the concentration curve of both parent drugs and metabolites. This may necessitate a dose reduction to 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours in some patients. Quinupristin and dalfopristin are not metabolized by cytochrome P450 enzymes but significantly inhibit CYP 3 A4, which metabolizes warfarin, diazepam, astemizole, terfenadine, cisapride, nonnucleo- side reverse transcriptase inhibitors, and cyclosporine, among others. Dosage reduction of cyclosporine may be necessary. 

The major oxidative drug-metabolizing pathway is catalyzed by cytochrome P450 enzymes (Mulder, 2006). The abbreviation CYP is typically used in this context. More than 60 CYPs have been identified. These are identified by up to four characters (letters or numbers). For example, in the term CYP2A4 4 the letters and numbers indicate the following ... 

Cidesonide is an agent that is inactive until it reaches its target site - the lung - where it is converted to its active metabolite des-isobutyryl-ciclesonide, catalyzed by esterases in the lung, whereas further metabolism of des-isobutyryl-ddesonide to inactive metabolites occurs in the liver and is catalyzed by cytochrome P450 enzymes, especially by CYP 3A4. 

---