ArticleBritish journal of clinical pharmacology2019
Plasma extracellular nanovesicle (exosome)-derived biomarkers for drug metabolism pathways: a novel approach to characterize variability in drug exposure.
Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Data-driven personalization of a physiologically based pharmacokinetic model for caffeine: A systematic assessment.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Advancing Pregnancy and Pediatric Science through the NIH Transporter Elucidation Network.Clinical pharmacology and therapeutics · 2026Review
- Review
- The New Spine of Access to the Brain's Secrets: Extracellular Vesicles from Cerebrospinal Fluid Liquid Biopsies in CNS Diseases and Blood-Brain Barrier Research.Molecular neurobiology · 2026Review
- Extracellular Vesicles as Enabling Biomarkers for New Approach Methodologies to Support the US Food and Drug Administration Modernization Act 3.0.Journal of extracellular vesicles · 2026Review
- A liquid biopsy-RNAseq method for monitoring the expression of genes involved in drug disposition: Proof-of-concept application to cholestatic liver disease.Journal of pharmaceutical and biomedical analysis · 2026Article
- The biology, function, and applications of exosomes as novel biomarkers forFrontiers in pharmacology · 2026Review
- The Role of Exosomal Biomarkers in the Monitoring of Bioactivation and Metabolite Clearance of Chemotherapeutics in Cancer Patients.Current drug metabolism · 2026Review
- Quantitation of Plasma Proteins to Predict Taxane-Induced Peripheral Neuropathy.JCO precision oncology · 2025Article
- 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
- Extracellular vesicles as the next-generation modulators of pharmacokinetics and pharmacodynamics of medications and their potential as adjuvant therapeutics.Clinical and translational medicine · 2024Review
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Article
- Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality.Life (Basel, Switzerland) · 2023Review
- A Physiologically Based Pharmacokinetic Model to Predict Determinants of Variability in Epirubicin Exposure and Tissue Distribution.Pharmaceutics · 2023Article
- The impact ofFrontiers in pharmacology · 2023Article
- Isolation and Identification of Plasma Extracellular Vesicles Protein Biomarkers.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The Role of Extracellular Vesicles in Liver Pathogenesis.The American journal of pathology · 2022Review
- Possible Role of Extracellular Vesicles in Hepatotoxicity of Acetaminophen.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsDemonstrate the presence of cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) proteins and mRNAs in isolated human plasma exosomes and evaluate the capacity for exosome-derived biomarkers to characterize variability in CYP3A4 activity.
methodsThe presence of CYP and UGT protein and mRNA in exosomes isolated from human plasma and HepaRG cell culture medium was determined by mass spectrometry and reverse transcription-polymerase chain reaction, respectively. The concordance between exosome-derived CYP3A4 biomarkers and midazolam apparent oral clearance (CL/F) was evaluated in a small proof-of-concept study involving six genotyped (CYP3A4 *1/*1 and CYP3A5 *3/*3) Caucasian males.
resultsExosomes isolated from human plasma contained peptides and mRNA originating from CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2 J2, 3A4 and 3A5, UGT 1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B10 and 2B15, and NADPH-cytochrome P450 reductase. Mean (95% confidence interval) exosome-derived CYP3A4 protein expression pre- and post-rifampicin dosing was 0.24 (0.2-0.28) and 0.42 (0.21-0.65) ng ml
conclusionsConsistent strong concordance was observed between exosome-derived CYP3A4 biomarkers and midazolam CL/F. The significance of these results is that CYP3A4 is the drug-metabolizing enzyme of greatest clinical importance and variability in CYP3A4 activity is poorly described by existing precision dosing strategies.
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