ArticleClinical pharmacology and therapeutics2021
Liquid Biopsy Enables Quantification of the Abundance and Interindividual Variability of Hepatic Enzymes and Transporters.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- PBPK modeling: What is the role of CYP3A4 expression in the gastrointestinal tract to accurately predict first-pass metabolism?CPT: pharmacometrics & systems pharmacology · 2025Pooled it
- 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
- Predicting Pharmacokinetic Variability and Drug Interaction Risk Using Omics-Based Biomarkers.Clinical and translational science · 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
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- 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
- Drug Interaction PBPK Modeling: Review of the Literature Exposes the Need for Increased Verification of Model Inputs and Outputs as Part of Credibility Assessment.Clinical and translational science · 2025Review
- Organic anion transporting polypeptides: Pharmacology, toxicology, structure, and transport mechanisms.Pharmacological reviews · 2025Review
- Extracellular vesicles efficiently deliver survival motor neuron protein to cells in culture.Scientific reports · 2025Article
- 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
- A close examination of BCRP's role in lactation and methods for predicting drug distribution into milk.CPT: pharmacometrics & systems pharmacology · 2024Review
- Effect of Food Composition on the PK of Isoniazid Quantitatively Explained Using Physiologically Based Biopharmaceutics Modeling.The AAPS journal · 2024Article
- Extracellular Vesicles as Surrogates for the Regulation of the Drug Transporters ABCC2 (MRP2) and ABCG2 (BCRP).International journal of molecular sciences · 2024Article
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Binding of Per- and Polyfluoroalkyl Substances (PFAS) to Serum Proteins: Implications for Toxicokinetics in Humans.Environmental science & technology · 2024Article
- Composition, functions, and applications of exosomal membrane proteins.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Variability in individual capacity for hepatic elimination of therapeutic drugs is well recognized and is associated with variable expression and activity of liver enzymes and transporters. Although genotyping offers some degree of stratification, there is often large variability within the same genotype. Direct measurement of protein expression is impractical due to limited access to tissue biopsies. Hence, determination of variability in hepatic drug metabolism and disposition using liquid biopsy (blood samples) is an attractive proposition during drug development and in clinical practice. This study used a multi-"omic" strategy to establish a liquid biopsy technology intended to assess hepatic capacity for metabolism and disposition in individual patients. Plasma exosomal analysis (n = 29) revealed expression of 533 pharmacologically relevant genes at the RNA level, with 147 genes showing evidence of expression at the protein level in matching liver tissue. Correction of exosomal RNA expression using a novel shedding factor improved correlation against liver protein expression for 97 liver-enriched genes. Strong correlation was demonstrated for 12 key drug-metabolizing enzymes and 4 drug transporters. The developed test allowed reliable patient stratification, and in silico trials demonstrated utility in adjusting drug dose to achieve similar drug exposure between patients with variable hepatic elimination. Accordingly, this approach can be applied in characterization of volunteers prior to enrollment in clinical trials and for patient stratification in clinical practice to achieve more precise individual dosing.
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