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. 2019 Jul;8(7):511-519.
doi: 10.1002/psp4.12417. Epub 2019 Jun 17.

The Cancer Drug Fraction of Metabolism Database

Liyan Hua  1 , Chien-Wei Chiang  2 , Wang Cong  1 , Jin Li  1 , Xueying Wang  1 , Lijun Cheng  2 , Weixing Feng  1 , Sara K Quinney  3   4 , Lei Wang  1   2 , Lang Li  2
Affiliations

The Cancer Drug Fraction of Metabolism Database

Liyan Hua et al. CPT Pharmacometrics Syst Pharmacol. 2019 Jul.

Abstract

This study aims to create a database for quantifying the fraction of metabolism of cytochrome P450 isozymes for cancer drugs approved by the US Food and Drug Administration. A reproducible data collection protocol was developed to extract essential information, including both substrate-depletion and metabolite-formation data from publicly available in vitro selective cytochrome P450 enzyme inhibition studies. We estimated the fraction of metabolism from the curated data. To demonstrate the utility of this database, we conducted an in vitro drug interaction prediction for the 42 cancer drugs. In the drug-drug interaction prediction, we identified 31 drug pairs with at least one cancer drug in each pair that had predicted area under concentration ratios > 2. We further found clinical drug interaction pieces of evidence in the literature to support 20 of these 31 drug-drug interaction pairs.

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Conflict of interest statement

The authors declared no competing interests for this work. As an Associate Editor for CPT: Pharmacometrics & Systems Pharmacology, Lang Li was not involved in the review or decision process for this article.

Figures

Figure 1
Figure 1
The flowchart of data‐collection procedure. Fm, fraction of metabolism.
Figure 2
Figure 2
The validation results: (a) The consistency evaluation results between original annotator and validation annotator1; (b) The consistency evaluation results between original annotator and validation annotator2; (c) The validation results between original annotator and finalized annotator. the different colors represent different cytochrome P450 enzymes, and the different shapes represent different drugs. The flash line represents the equality of the horizontal and vertical axes. The horizontal axis represents original annotator, and the vertical axes represent validation annotator 1, validation annotator 2, and finalized annotation.
See this image and copyright information in PMC

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