The human drug metabolizing cytochromes P450.
The superfamily of heme-thiolate proteins known as the cytochromes P450 is responsible for the oxidative metabolism of the majority of drugs. Thus, the phenotypes of individuals with respect to their levels of catalytically active cytochromes P450 determines to a large part the substantial interindividual variation observed in the metabolic clearance of drugs. Over the past 10 years 15 different human cytochromes P450 involved in drug metabolism have been isolated and characterized to varying degrees. This brief review discusses the characterization of these cytochromes P450 and how this knowledge has been used by the pharmaceutical industry to aid in the development of new drugs.
Wrighton
S A
SA
Department of Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
VandenBranden
M
M
Ring
B J
BJ
D001572:Benzofurans / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D015195:Drug Design; D004790:Enzyme Induction / Q000502:physiology; D014644:Genetic Variation; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010641:Phenotype; D012702:Serotonin Antagonists / Q000378:metabolism
D001572:Benzofurans; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004364:Pharmaceutical Preparations; D012702:Serotonin Antagonists; C064877:zatosetron; D003577:Cytochrome P-450 Enzyme System