Identification of genetic biomarkers associated with pharmacokinetics and pharmacodynamics of apixaban in Chinese healthy volunteers.

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 variants were associated with C and AUC of apixaban (p < 6.12 × 10) and also presented significant differences of anti-Xa activity and dPT according to different genotypes (p < 0.05). Besides, variants were found to be associated with PK characteristics and and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10).

CONCLUSION

variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. and were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399.