ArticleBritish journal of clinical pharmacology2024
Establishing the capacity to monitor proteins relevant to the study of drug exposure and response using liver-derived extracellular vesicles.
Article in British journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The trial behind it
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Who cites it
3 citing papers in PubMed.
- Circulating Extracellular Vesicles Reflect Dynamic Shifts in Liver Transcriptome Following Tumour Resection.Cancers · 2026Article
- Detection and Isolation of Tissue-Specific Extracellular Vesicles From the Blood.Journal of extracellular biology · 2025Review
- Establishing the capacity to monitor proteins relevant to the study of drug exposure and response using liver-derived extracellular vesicles.British journal of clinical pharmacology · 2024Article
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Authors and funding
5 authors.
Funding
Abstract
aimsDrug exposure and response is determined by pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Interindividual differences in abundance of drug metabolizing enzymes (DMEs) and drug target proteins underpin PK and PD variability and impact treatment efficacy and tolerability. Extracellular vesicles (EVs) carry protein cargo inherited from originating cells and may be useful for defining differences in key proteins related to hepatic drug metabolism and the treatment of metabolic-associated fatty liver disease (MAFLD). We sought to quantify these proteins in liver-derived EVs and establish the profile relative to paired tissue.
methodsEVs were recovered from human liver tissue samples (LT-EV, n = 11). Targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays were employed for absolute quantification of proteins in EV isolates and matched liver tissue.
resultsDMEs and MAFLD drug targets were readily detected and quantified in LT-EVs. Twelve of 15 DMEs exhibited moderate to strong correlation (Spearman ⍴ = 0.618-0.973) between tissue and EVs. Correlation in protein abundance was influenced by the extent of extra-hepatic expression of the target.
conclusionsThis study provides evidence that key proteins related to PK and PD profiles can be measured in liver-derived EVs and abundance of liver-enriched DMEs are robustly correlated between paired tissue and EVs. The robust detection of protein markers related to drug PD profile in MAFLD opens the possibility to track within-subject changes in MAFLD and lays the foundation for future development of a liver-derived EV liquid biopsy to assess markers of drug exposure and response in vivo.
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