Reaction phenotyping: current industry efforts to identify enzymes responsible for metabolizing drug candidates.
Reaction phenotyping studies to identify specific enzymes involved in the metabolism of drug candidates are increasingly important in drug discovery efforts. Experimental approaches used for CYP reaction phenotyping include incubations with cDNA expressed CYP enzyme systems and incubations containing specific CYP enzyme inhibitors. Since both types of experiments present specific advantages as well as known drawbacks, these studies are generally viewed as complementary approaches. Although glucuronidation pathways are also known to present potential drug-drug interaction issues as well as challenges related to their polymorphic expression, reaction phenotyping approaches for glucuronidation are generally limited to cDNA expressed systems due to lack of availability of specific UGT inhibitors. This article presents a limited review of current approaches to reaction phenotyping studies used within the pharmaceutical industry.
Harper
Timothy W
TW
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb, PO Box 5400, Mail Stop 17-12, Princeton, New Jersey 08543-5400, USA. timothy.harper@bms.com
Brassil
Patrick J
PJ
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004345:Drug Industry / Q000379:methods* / Q000639:trends; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010641:Phenotype
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System