Inflammatory protein signatures associated with high rivaroxaban exposure
Abstract
Direct oral anticoagulants, including rivaroxaban, are widely prescribed for the prevention and treatment of thromboembolic disorders. Despite generally predictable pharmacokinetics (PK), real-world data reveal striking interindividual variability in exposure, raising concerns for both efficacy and bleeding risk. Known genetic and clinical determinants explain only part of this variability, underscoring the need to identify additional contributors. This study aimed to explore systemic protein signatures associated with rivaroxaban exposure intensity. Plasma samples were obtained from 64 participants in a phase I clinical study (NCT04180436) including healthy controls, obese patients, and post-bariatric surgery patients. Rivaroxaban PK was assessed after 20 mg once-daily dosing, and patients were stratified into high and low exposure groups. Untargeted plasma proteomic analysis was performed by liquid chromatography coupled with high-resolution mass spectrometry, followed by Abbreviations: A30, Protein A30; ABCB1, ATP-binding cassette sub-family B member 1 gene; ABI3, ABI Family Member 3; ADAMTS13, A disintegrin and metalloproteinase with thrombospondin motifs 13; AGT, Angiotensinogen; ALB, Albumin; anti-EDB-scFv, Single-chain variable fragment anti-EDB; APOB, Apolipoprotein B; APOE, Apolipoprotein E; AUC_D1, Area under the concentration-time curve at day 1 after the first dose; AUC_SS, Area under the concentration-time curve at steady state; BER, Balanced error rate; BST1, Bone marrow stromal cell antigen 1; C7, Complement component 7; CC1, Complement component 1; CD5L, CD5 Antigen-Like; CDHR2, Cadherin-related family member 2; CHL1, Close homolog of L1; Cmax_D1, Maximum plasma concentration at day 1 after the first dose; Cmax_SS, Maximum plasma concentration at steady state; COL6A3, Collagen type VI alpha 3 Chain; COLEC10, Collectin subfamily member 10; CRP, C-reactive protein; CRISP3, Cysteine-rich secretory protein 3; CSF1R, Colony-stimulating factor 1 receptor; CST3, Cystatin C; CTSD,
Related
- Nicotinamide Mononucleotide Is Associated with Attenuation of OGD/R-Induced Pro-Inflammatory Programs in Microglia: Transcriptomic Evidence Converging on the NLRP3 Inflammasome and Lipid-Droplet-Related Molecular Signatures
- SCO2, LYN, and FGR as Mitochondria-Associated Immune-Inflammatory Candidate Signatures Across PMOS and MCI Datasets
- Prior Ustekinumab Exposure and Ulcerative Colitis Are Associated with Suboptimal Trough Levels in Patients Receiving Advanced-Line Vedolizumab or Ustekinumab for Inflammatory Bowel Disease: A Cross-Sectional Cohort Study
- Integrated Transcriptomic and Single-Cell Analysis Reveals Shared Macrophage-Associated Inflammatory Signatures in MASLD/NAFLD and Rheumatoid Arthritis
- Systemic cytokine signatures associated with volcanic emisions exposure and respiratory disease after the cumbre vieja eruption-ashes project
BibTeX
@article{feliu2026inflammatory,
title = {{Inflammatory protein signatures associated with high rivaroxaban exposure}},
author = {Catherine Feliu and Jean Escal and Cyril Leven and Sophie Hodin and Vanessa Rigaud and Philippe Gonzalo and Francis Coutureau and Karine Lacut and Jeremy Thereaux and Xavier Delavenne},
journal = {Biochemical Pharmacology},
year = {2026},
month = sep,
doi = {10.1016/j.bcp.2025.117663},
url = {https://univ-brest.hal.science/hal-05733571v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Inflammatory protein signatures associated with high rivaroxaban exposure
AU - Catherine Feliu
AU - Jean Escal
AU - Cyril Leven
AU - Sophie Hodin
AU - Vanessa Rigaud
AU - Philippe Gonzalo
AU - Francis Coutureau
AU - Karine Lacut
AU - Jeremy Thereaux
AU - Xavier Delavenne
PY - 2026
DA - 2026/09/01
JO - Biochemical Pharmacology
DO - 10.1016/j.bcp.2025.117663
UR - https://univ-brest.hal.science/hal-05733571v1
AB - Direct oral anticoagulants, including rivaroxaban, are widely prescribed for the prevention and treatment of thromboembolic disorders. Despite generally predictable pharmacokinetics (PK), real-world data reveal striking interindividual variability in exposure, raising concerns for both efficacy and bleeding risk. Known genetic and clinical determinants explain only part of this variability, underscoring the need to identify additional contributors. This study aimed to explore systemic protein signatures associated with rivaroxaban exposure intensity. Plasma samples were obtained from 64 participants in a phase I clinical study (NCT04180436) including healthy controls, obese patients, and post-bariatric surgery patients. Rivaroxaban PK was assessed after 20 mg once-daily dosing, and patients were stratified into high and low exposure groups. Untargeted plasma proteomic analysis was performed by liquid chromatography coupled with high-resolution mass spectrometry, followed by Abbreviations: A30, Protein A30; ABCB1, ATP-binding cassette sub-family B member 1 gene; ABI3, ABI Family Member 3; ADAMTS13, A disintegrin and metalloproteinase with thrombospondin motifs 13; AGT, Angiotensinogen; ALB, Albumin; anti-EDB-scFv, Single-chain variable fragment anti-EDB; APOB, Apolipoprotein B; APOE, Apolipoprotein E; AUC_D1, Area under the concentration-time curve at day 1 after the first dose; AUC_SS, Area under the concentration-time curve at steady state; BER, Balanced error rate; BST1, Bone marrow stromal cell antigen 1; C7, Complement component 7; CC1, Complement component 1; CD5L, CD5 Antigen-Like; CDHR2, Cadherin-related family member 2; CHL1, Close homolog of L1; Cmax_D1, Maximum plasma concentration at day 1 after the first dose; Cmax_SS, Maximum plasma concentration at steady state; COL6A3, Collagen type VI alpha 3 Chain; COLEC10, Collectin subfamily member 10; CRP, C-reactive protein; CRISP3, Cysteine-rich secretory protein 3; CSF1R, Colony-stimulating factor 1 receptor; CST3, Cystatin C; CTSD,
SN - 0006-2952
SN - 1873-2968
ER -