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Treffer: Pharmaceutical Metabolite Data Base, PharmMet DB: Reference data base for drug metabolites generated by human liver S9 fraction.

Title:
Pharmaceutical Metabolite Data Base, PharmMet DB: Reference data base for drug metabolites generated by human liver S9 fraction.
Authors:
Jeon J; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia; Graduate Division of Biological and Biomedical Sciences, Molecular and Systems Pharmacology, Emory University, Atlanta, Georgia., Jarrell ZR; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia., Lee CM; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia., Singer G; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia; Graduate Division of Biological and Biomedical Sciences, Molecular and Systems Pharmacology, Emory University, Atlanta, Georgia., Weinberg J; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia; Graduate Division of Biological and Biomedical Sciences, Molecular and Systems Pharmacology, Emory University, Atlanta, Georgia., Liu KH; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia., Morgan ET; Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, Georgia., Go YM; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia., Jones DP; Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia. Electronic address: dpjones@emory.edu.
Source:
Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2025 Nov; Vol. 53 (11), pp. 100183. Date of Electronic Publication: 2025 Oct 13.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9421550 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-009X (Electronic) Linking ISSN: 00909556 NLM ISO Abbreviation: Drug Metab Dispos Subsets: MEDLINE
Imprint Name(s):
Publication: 2025- : [Amsterdam] : Elsevier
Original Publication: [Bethesda, Md., etc., American Society for Pharmacology and Experimental Therapeutics, etc.]
MeSH Terms:
Liver*/metabolism , Databases, Pharmaceutical*, Humans ; Pharmaceutical Preparations/metabolism ; Chromatography, Liquid/methods ; Drug Monitoring/methods ; Microsomes, Liver/metabolism ; Databases, Factual ; Mass Spectrometry/methods ; Biotransformation
Contributed Indexing:
Keywords: Drug acetylation; Drug glutathionylation; Drug metabolism; Drug oxidation; Drug sulfation; PharmMet DB
Substance Nomenclature:
0 (Pharmaceutical Preparations)
Entry Date(s):
Date Created: 20251104 Date Completed: 20251123 Latest Revision: 20251123
Update Code:
20251124
DOI:
10.1016/j.dmd.2025.100183
PMID:
41187514
Database:
MEDLINE

Weitere Informationen

Drug monitoring is an essential component of precision therapeutics, yet existing data bases to support therapeutic monitoring are limited to data curated from the scientific literature or predicted in silico. We used human liver S9 fraction to generate metabolites from 1114 therapeutic drugs spanning diverse drug classes. Metabolites were analyzed by liquid chromatography-high-resolution mass spectrometry, annotated through differential analysis of preincubation and postincubation samples, curated by comparison to predicted metabolites from BioTransformer 3.0, and compiled into a human liver pharmaceutical metabolite resource, named "Pharmaceutical Metabolite Data Base (PharmMet DB)." Liquid chromatography-high-resolution mass spectrometry showed heterogeneity in product generation, with some drugs mostly being converted to predicted metabolites, while others were converted to hundreds of unpredicted products characterized by mass-to-charge ratio and chromatographic retention time. Phase I metabolism was dominant, with 30,752 oxidized drug metabolites. Glucuronidation was dominant for phase II metabolism, with 6311 drug metabolites. Notably, 89% of tested drugs produced at least 1 metabolite that was not predicted on BioTransformer 3.0, and these novel metabolites were most frequently detected for anti-inflammatory, central nervous system and antimicrobial drug classes. PharmMet DB provides experimental metabolite profiles to detect therapeutic drug exposures in human biospecimens without a requirement for prescription history. PharmMet DB usage with human epidemiology will advance pharmacometabolomics to improve understanding of drug efficacy, adverse reactions, and interactions in precision medicine. SIGNIFICANCE STATEMENT: Pharmaceutical Metabolite Data Base is a new data base of therapeutic drug metabolites suitable for use with liquid chromatography-high-resolution mass spectrometry to monitor patient adherence, detect unreported drug use, for example, in clinical trials, and enhance pharmacoexposomics and pharmacogenomics research. The data base was generated by incubation of therapeutic agents with human liver S9 fraction and curated relative to in silico predicted metabolites. Associated metadata for metabolic processes and drug classes enhance utility for clinical use, especially with untargeted metabolomics analyses of human samples.
(Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Conflict of interest The authors declare no conflicts of interest.