clinical pharmacology
Drug Metabolism
Cytochrome P 450
The most important enzyme system of phase I metabolism is cytochrome P-450 (CYP450), a microsomal superfamily of isoenzymes that catalyzes the oxidation of many drugs. The electrons are supplied by NADPH–CYP450 reductase, a flavoprotein that transfers electrons from NADPH (the reduced form of nicotinamide adenine dinucleotide phosphate) to CYP450. CYP450 enzymes can be induced or inhibited by many drugs and substances resulting in drug interactions in which one drug enhances the toxicity or reduces the therapeutic effect of another drug. For examples of drugs that interact with specific enzymes, see tables Common Substances That Interact With Cytochrome P-450 Enzymes and 30% because hepatic volume and blood flow are decreased. Thus, drugs that are metabolized through this system reach higher levels and have prolonged half-lives in older people (see figure Comparison of pharmacokinetic outcomes for diazepam in a younger man (A) and an older man (B) ). Because neonates have partially developed hepatic microsomal enzyme systems, they also have difficulty metabolizing many drugs. 