Microsomal P450 systems, in which electrons are transferred from NADPH via cytochrome P450 reductase (variously CPR, POR, or CYPOR). Cytochrome b 5 (cyb 5 ) can also contribute reducing power to this system after being reduced by cytochrome b 5 reductase (CYB 5 R). Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most. pharma-flash volume 29, n°4, 2002 15 interactions medicamenteuses et cytochromes p450 1a2 2b6 2c9 2c19 2d6 2e13a4 1a2 2b6 2c9 2c19 2d6 3a4 1a2 2b6 2c9 2c19 2d6 2e1 3a4 Introduction. The cytochrome P450 (P450 or CYP) isoenzymes are a group of heme-containing enzymes embedded primarily in the lipid bilayer of the endoplasmic reticulum of hepatocytes, it takes part in the metabolism of many drugs, steroids and carcinogens. The most intensively studied route of drug metabolism is the P450-catalysed. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes (data only for antifungal). Some 100 therapeutic drugs are metabolized by CYP2C9, including drugs with a narrow therapeutic index such as warfarin and phenytoin and other routinely prescribed drugs such as acenocoumarol , tolbutamide , losartan , glipizide , and some nonsteroidal anti-inflammatory drugs. The anticoagulant drug warfarin occurs as a pair of enantiomers that are differentially metabolized by human cytochromes P450 (CYP). R-warfarin is metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10-hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols. designation of specific cytochrome P450 isoforms. A drug appears in a column if there is published evidence that it is metabolized, at least in part, via that isoform. It does not necessarily follow that the isoform is the principal metabolic pathway in vivo, or that alterations in the rate of the metabolic reaction catalyzed by that isoform will have large effects on the pharmacokinetics of. Pharmacokinetic Interactions. The most common manifestation of pharmacokinetic interactions with warfarin involves the inhibition or induction of its metabolism. The cytochrome P450 system is an evolutionary system to deal with the breakdown of endogenous and exogenous chemicals in the body. There is an increasing amount of interest in this area as new information is enabling us to understand why people metabolise drugs differently and why there is a Drug metabolism via the cytochrome P450 system has emerged as an important determinant in the occurrence of several drug-drug interactions. A greater degree of interaction predictability has been achieved through the identification of P450 isozymes and some of the drugs that share them.