title: Expression of hepatic drug-metabolizing cytochrome p450 enzymes and their intercorrelations: a meta-analysis.
abstract: Cytochrome P450 is a family of enzymes that catalyze reactions involved in the metabolism of drugs and other xenobiotics. These enzymes are therefore important in pharmacologic and toxicologic studies, and information on their abundances is of value in the process of scaling in vitro data to in vivo metabolic parameters. A meta-analysis was applied to data on the abundance of human hepatic cytochrome P450 enzymes in Caucasian adult livers (50 studies). Despite variations in the methods used to measure the abundance of enzymes, agreement between the studies in 26 different laboratories was generally good. Nonetheless, some heterogeneity was detected (Higgins and Thompson heterogeneity test). More importantly, large interindividual variability was observed in the collated data. Positive correlations between the expression levels of some cytochrome P450 enzymes were found in the abundance data, including the following pairs: CYP3A4/CYP3A5*1/*3 (Rs = 0.70, P < 0.0001, n = 52), CYP3A4/CYP2C8 (Rs = 0.68, P < 0.0001, n = 134), CYP3A4/CYP2C9 (Rs = 0.55, P < 0.0001, n = 71), and CYP2C8/CYP2C9 (Rs = 0.55, P < 0.0001, n = 99). These correlations can be used to demonstrate common genetic transcriptional mechanisms.
authors.affiliation: Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom (B.A., J.B., A.R-H.), and Simcyp Limited, a Certara Company, Sheffield, United Kingdom (A.R-H.).
authors.forename: Brahim
authors.initials: B
authors.lastname: Achour
authors.affiliation: Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom (B.A., J.B., A.R-H.), and Simcyp Limited, a Certara Company, Sheffield, United Kingdom (A.R-H.).
authors.forename: Jill
authors.initials: J
authors.lastname: Barber
authors.affiliation: Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom (B.A., J.B., A.R-H.), and Simcyp Limited, a Certara Company, Sheffield, United Kingdom (A.R-H.) amin.rostami@manchester.ac.uk.
authors.forename: Amin
authors.initials: A
authors.lastname: Rostami-Hodjegan
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007206:Individuality; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism
chemical_list: D003577:Cytochrome P-450 Enzyme System