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Abundance and Associated Variations of Cytochrome P450 Drug-Metabolizing Enzymes in the Liver of East Asian Adults: A Meta-Analysis

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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.

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Authors and Affiliations

  1. Clinical Medical College, Yangzhou University, Yangzhou, China

    Xiao-Xiao An, Guo-Fu Li & Guo Yu

  2. Institution of Drug Clinical Trial, Subei People’s Hospital, Yangzhou, China

    Xiao-Xiao An, Guo-Fu Li & Guo Yu

  3. College of Pharmacy, Dalian Medical University, Dalian, China

    Xiao-Xiao An

  4. Department of Pharmaceutics, University of Florida, Gainesville, FL, 32608, USA

    Yichao Yu

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  1. Xiao-Xiao An
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Correspondence to Guo Yu.

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Funding

Guo Yu was supported in part by the National Natural Science Foundation of China (no. 81603209) and Jiangsu Provincial Science Fund for Distinguished Young Scholars (BK20200005) for the conduct of this study. The funding organization played no role in the preparation, review, or approval of the manuscript.

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Xiao-Xiao An, Yichao Yu, Guo-Fu Li, Guo Yu have no conflicts of interest that are directly relevant to the contents of this manuscript.

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An, XX., Yu, Y., Li, GF. et al. Abundance and Associated Variations of Cytochrome P450 Drug-Metabolizing Enzymes in the Liver of East Asian Adults: A Meta-Analysis. Eur J Drug Metab Pharmacokinet 46, 225–233 (2021). https://doi.org/10.1007/s13318-020-00667-9

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