RT Journal Article
SR Electronic
T1 Antibodies as a Probe in Cytochrome P450 Research
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 925
OP 931
DO 10.1124/dmd.108.025718
VO 37
IS 5
A1 Magang Shou
A1 Anthony Y. H. Lu
YR 2009
UL http://dmd.aspetjournals.org/content/37/5/925.abstract
AB Cytochrome P450 (P450) is the superfamily of enzymes responsible for biotransformation of endobiotics and xenobiotics. However, their large isoform multiplicity, inducibility, diverse structure, widespread distribution, polymorphic expression, and broad overlapping substrate specificity make it difficult to measure the precise role of each individual P450 to the metabolism of drugs (or carcinogens) and hamper the understanding of the relationship between the genetic/environmental factors that regulate P450 phenotype and the responses of the individual P450s to drugs. The antibodies against P450s have been useful tools for the quantitative determination of expression level and contribution of the epitope-specific P450 to the metabolism of a drug or carcinogen substrate in tissues containing multiple P450 isoforms and for implications in pharmacogenetics and human risk assessment. In particular, the inhibitory antibodies are uniquely suited for reaction phenotyping that helps to predict human pharmacokinetics for clinical drug-drug interaction potential in drug discovery and development. The American Society for Pharmacology and Experimental Therapeutics