Session: Session 2
Pharmacoproteomic approach to explore variability rivaroxaban exposure
Introduction: Pharmacoproteomics is an original approach of pharmacology that focuses on the large-scale study of proteins to better understand drug exposure variability. A previous pharmacokinetic study about rivaroxaban in obese and bariatric surgery subjects revealed large inter-individual variability. The aim of this new study was to perform proteomic profiling to identify potential biomarkers for predicting rivaroxaban exposure.
Methodology: Patients from the initial study (ABSORB) were selected for proteomic analysis. This phase 1 study included four groups of patients: 1) obese patients with a BMI ≥ 40 kg/m², 2) patients with a history of RYGB, 3) patients with a history of SG, and 4) a control group. Plasma samples were collected for proteomic analysis before initiating rivaroxaban treatment. Untargeted protein identification using liquid chromatography coupled with high-resolution mass spectrometry was performed. Differences in protein expression were studied with Perseus and R software tools.
Results: The 64 patients were classified into three groups according to their respective AUC of rivaroxaban in blood. High AUCs ranged from 2221 to 3712 (n=16), median AUCs ranged from 1507 to 2198 (n=32), and low AUCs ranged from 764 to 1439 (n=16). The highest and lowest AUC groups were compared. Analysis revealed that inflammation proteins were statistically more expressed in the high AUC group compared to the low AUC group, including C-reactive protein and leukotriene A4 hydrolase.
Conclusion: CRP was identified as a potential marker of risk of overexposure to Rivaroxaban, with a potential risk of adverse events, particularly bleeding events. Inflammation has already been described in the literature as influencing drug response variability by altering the regulation of drug metabolizing enzymes and transporters in humans. The next step is to confirm CRP involvement in variability rivaroxaban exposure.
Methodology: Patients from the initial study (ABSORB) were selected for proteomic analysis. This phase 1 study included four groups of patients: 1) obese patients with a BMI ≥ 40 kg/m², 2) patients with a history of RYGB, 3) patients with a history of SG, and 4) a control group. Plasma samples were collected for proteomic analysis before initiating rivaroxaban treatment. Untargeted protein identification using liquid chromatography coupled with high-resolution mass spectrometry was performed. Differences in protein expression were studied with Perseus and R software tools.
Results: The 64 patients were classified into three groups according to their respective AUC of rivaroxaban in blood. High AUCs ranged from 2221 to 3712 (n=16), median AUCs ranged from 1507 to 2198 (n=32), and low AUCs ranged from 764 to 1439 (n=16). The highest and lowest AUC groups were compared. Analysis revealed that inflammation proteins were statistically more expressed in the high AUC group compared to the low AUC group, including C-reactive protein and leukotriene A4 hydrolase.
Conclusion: CRP was identified as a potential marker of risk of overexposure to Rivaroxaban, with a potential risk of adverse events, particularly bleeding events. Inflammation has already been described in the literature as influencing drug response variability by altering the regulation of drug metabolizing enzymes and transporters in humans. The next step is to confirm CRP involvement in variability rivaroxaban exposure.