Key result
ABCG2 variants are linked to apixaban Cmax, AUC, and anti-Xa activity.
Why the study?
Apixaban exhibits interindividual variability in concentration and response in the real world, and genetic biomarkers associated with its pharmacokinetics and pharmacodynamics in healthy Chinese subjects remained to be identified.
Are genetic biomarkers associated with the pharmacokinetics and pharmacodynamics of apixaban in healthy Chinese adults?
Observational (n=181)
Yes
Are genetic biomarkers associated with the pharmacokinetics and pharmacodynamics of apixaban in healthy Chinese adults?
p-value: p=< 6.12 × 10−5
Genetic variants in ABCG2, ABLIM2, F13A1, and C3 are associated with inter-individual variability in apixaban pharmacokinetics and pharmacodynamics.
Genetic variants may affect apixaban PK/PD in Chinese subjects; leaves open personalized dosing pending clinical validation.
Background Apixaban is a superior direct oral anticoagulant exihibiting interindividual variability in concentration and response in the real world. The present study aimed to identify genetic biomarkers associated with pharmacokinetics (PK) and pharmacodynamics (PD) of apixaban in healthy Chinese subjects.Methods This multicenter study included 181 healthy Chinese adults taking a single dose of 2.5 mg or 5 mg apixaban and assessed their PK and PD parameters. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed using the Affymetrix Axiom CBC_PMRA Array. Candidate gene association analysis and genome-wide association study were conducted to identify genes with a predictive value for PK and PD parameters of apixaban.Results Several ABCG2 variants were associated with Cmax and AUC0-t of apixaban (p < 6.12 × 10−5) and also presented significant differences of anti-Xa3h activity and dPT3h according to different ABCG2 genotypes (p < 0.05). Besides, ABLIM2 variants were found to be associated with PK characteristics and F13A1 and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10−8).Conclusion ABCG2 variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. ABLIM2, F13A1 and C3 were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399.
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Mu et al. (2023) conducted an observational in Healthy volunteers (n=181). Genetic variants (ABCG2, ABLIM2, F13A1, C3) vs. Alternative genotypes was evaluated on Pharmacokinetics (Cmax, AUC0-t) and pharmacodynamics (anti-Xa3h activity, dPT3h) of apixaban (p=< 6.12 × 10−5). ABCG2 variants were significantly associated with apixaban Cmax and AUC0-t (p < 6.12 × 10−5), as well as anti-Xa3h activity and dPT3h (p < 0.05).
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