Key result
ABCB1 rs2032582 G allele linked to ~26% lower rivaroxaban exposure in observational cohort.
Why the study?
Interindividual variability in rivaroxaban exposure remains incompletely understood and may contribute to differences in treatment outcomes, motivating an investigation into the associations between CYP3A4, CYP2J2, and ABCB1 gene polymorphisms, clinical factors, and rivaroxaban pharmacokinetics.
Do genetic polymorphisms in CYP3A4, CYP2J2, and ABCB1 and clinical factors affect rivaroxaban pharmacokinetics and coagulation parameters in patients with cardiovascular diseases receiving rivaroxaban 20 mg once daily?
Observational (n=66)
Do genetic polymorphisms in CYP3A4, CYP2J2, and ABCB1 and clinical factors affect rivaroxaban pharmacokinetics and coagulation parameters in patients with cardiovascular diseases receiving rivaroxaban 20 mg once daily?
In patients taking rivaroxaban, clinical factors such as impaired renal function, drug interactions (e.g., eplerenone), and biological sex significantly impact drug pharmacokinetics and coagulation parameters after multiple testing correction, whereas nominal genetic associations in ABCB1 and CYP3A4 require validation in larger cohorts.
Genotyping for these variants should not yet guide rivaroxaban dosing; leaves open their contribution to exposure variability.
Purpose: Interindividual variability in rivaroxaban exposure remains incompletely understood and may contribute to differences in treatment outcomes. This study aimed to investigate associations between polymorphisms in CYP3A4 (rs2242480), CYP2J2 (rs890293), and ABCB1 (rs1045642, rs2032582) genes, clinical factors and rivaroxaban pharmacokinetics. Methods: The study included 66 patients receiving 20 mg of rivaroxaban once daily. Rivaroxaban concentrations in plasma and dried blood spots were determined using a validated UPLC-MS/MS method. Genotyping was performed using PCR-RFLP. Associations between pharmacokinetic parameters, genetic variants and anthropometric characteristics, concomitant medications, comorbidities, and coagulation parameters were assessed using appropriate statistical analyses. Results: Carriers of the ABCB1 rs2032582 G allele exhibited lower rivaroxaban exposure, as reflected by reduced AUC0–12h values compared with non-carriers (1817.43 ± 703.70 vs. 2442.96 ± 691.13 ng·h/mL, nominal p = 0.0369). Concomitant use of eplerenone was associated with increased rivaroxaban exposure. Body mass composition and impaired renal function were associated with rivaroxaban concentrations. In addition, associations between CYP3A4 rs2242480 genotype and several body size descriptors, including body weight or lean body mass, and selected coagulation parameters were observed in exploratory analyses. However, most nominal associations did not remain statistically significant after correction for multiple comparisons. After Benjamini–Hochberg correction, only impaired renal function, drug interactions and biological sex remained statistically significant factors, impacting rivaroxaban’s pharmacokinetics and anticoagulant parameters. Conclusions: Several genetic and clinical factors showed nominal association with rivaroxaban pharmacokinetics and coagulation parameters in this study. These findings should be interpreted as exploratory given the limited sample size and the number of statistical comparisons. Further studies in larger cohorts are needed to clarify the clinical relevance of genetic and clinical determinants of rivaroxaban exposure.
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Pawlak et al. (2026) conducted an observational in Cardiovascular diseases treated with rivaroxaban (n=66). Polymorphisms in CYP3A4, CYP2J2, and ABCB1 genes and clinical factors vs. Non-carriers / reference genotypes and clinical profiles was evaluated on Rivaroxaban exposure (AUC0–12h, ng·h/mL) and coagulation parameters (p=0.0369 (nominal)). ABCB1 rs2032582 G allele carriers had lower rivaroxaban AUC0-12h vs non-carriers (1817.43 vs 2442.96 ng·h/mL, nominal p=0.0369), though only clinical factors survived multiple testing correction.
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