Cytochrome P450 enzyme turnover in vitro

Range 0.96 - 4.33 days
Organism Mammals
Reference Darwich AS, Aslam U, Ashcroft DM, Rostami-Hodjegan A. Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans. Drug Metab Dispos. 2014 Dec42(12):2016-22. doi: 10.1124/dmd.114.058404 abstract & p.2020 right column bottom paragraphPubMed ID25233858
Primary Source Yang et al. Cytochrome p450 turnover: regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab. 2008 Jun9(5):384-94.PubMed ID18537575
Method Abstract: "Current physiologically based pharmacokinetic (PBPK) models consider enzyme and enterocyte recovery as a lumped first-order rate. An assessment of enterocyte turnover would enable enzyme and enterocyte renewal to be modeled more mechanistically. A literature review together with statistical analysis was employed to establish enterocyte turnover in human and preclinical species."
Comments Abstract: "In mice, the geometric weighted combined mean (WX) enterocyte turnover was 2.81 ± 1.14 days (n = 169). In rats, the weighted arithmetic mean enterocyte turnover was determined to be 2.37 days (n = 501). Humans exhibited a geometric WX enterocyte turnover of 3.48 ± 1.55 days for the gastrointestinal epithelia (n = 265), displaying comparable turnover to that of cytochrome P450 enzymes in vitro (0.96-4.33 days)." P.2020 right column bottom paragraph: "The human enterocyte turnover, as determined in this analysis (approximately 3.48 days), suggests the GI [gastrointestinal] epithelia to display a comparable rate of renewal to that of the P450 enzymes as determined in vitro, in which Yang et al. (primary source) found reported P450 turnover to vary between 0.96 and 4.33 days."
Entered by Uri M
ID 113695