Article ; Online: Abundance and Associated Variations of Cytochrome P450 Drug-Metabolizing Enzymes in the Liver of East Asian Adults: A Meta-Analysis.
European journal of drug metabolism and pharmacokinetics
2020 Volume 46, Issue 2, Page(s) 225–233
Abstract: Background: Cytochrome P450 (CYP) enzymes are one of the main sources of variability in drug metabolic clearance. Information on their abundance levels is therefore crucial to optimize scaling factors for in vitro-in vivo extrapolation (IVIVE) to ... ...
| Abstract | Background: Cytochrome P450 (CYP) enzymes are one of the main sources of variability in drug metabolic clearance. Information on their abundance levels is therefore crucial to optimize scaling factors for in vitro-in vivo extrapolation (IVIVE) to predict metabolic clearance. Objective: This study aims to quantify the abundance data of hepatic drug-metabolizing CYP enzymes in East Asian subjects reported from various sources in the literature using meta-analysis. Method: We conducted a meta-analysis on the abundance of drug-metabolizing CYP enzymes in the liver of East Asian adults. Eligible reports were identified based on predefined criteria-(1) individual liver microsomal samples, and (2) absolute protein abundance data from normal tissues of East Asian adult subjects. Subgroup and sensitivity analyses were also performed. Results: Among the 11 CYP isoforms analyzed in East Asian subjects, CYP3A5 and CYP3A4 had the highest protein levels. In particular, the number of studies and the liver sample used to quantify the abundance of CYP3A4 were the largest. Of the isoforms involved, CYP2J2 and CYP2B6 had the lowest abundance level, i.e., <5 pmol/ mg of microsomal protein. For enzymes with abundance values available in both Chinese and Japanese subjects (CYP1A2, CYP2C9, CYP3A4, and CYP3A5), the abundance level of each CYP isoform appeared to be higher in Chinese than in Japanese subjects. The most distinct difference was observed in CYP3A5 abundance. Conclusion: The current meta-analysis shows that the abundance levels of CYP enzymes appear to vary greatly among different East Asian individuals who have similar ethnic backgrounds and food habits. The pooled data of CYP abundance can be used as preliminary reference values along with the associated variations for the projections of pharmacokinetics through physiologically based pharmacokinetic (PBPK) approaches. |
|---|---|
| MeSH term(s) | Adult ; Asian Continental Ancestry Group ; Cytochrome P-450 Enzyme System/metabolism ; Humans ; Liver/enzymology ; Microsomes, Liver/enzymology ; Pharmaceutical Preparations/metabolism |
| Chemical Substances | Pharmaceutical Preparations ; Cytochrome P-450 Enzyme System (9035-51-2) |
| Language | English |
| Publishing date | 2020-04-21 |
| Publishing country | France |
| Document type | Journal Article ; Meta-Analysis ; Systematic Review |
| ZDB-ID | 196729-0 |
| ISSN | 2107-0180 ; 0398-7639 ; 0378-7966 |
| ISSN (online) | 2107-0180 |
| ISSN | 0398-7639 ; 0378-7966 |
| DOI | 10.1007/s13318-020-00667-9 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 1236: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.