Drug interactions and pharmacogenetic factors contribute to variation in apixaban concentration in atrial fibrillation patients in routine care.
Markus GulilatDenise KellerBradley LintonA Demetri PananosDaniel LizotteGeorge K DresserJeffrey AlfonsiRommel G TironaRichard B KimUte I SchwarzPublished in: Journal of thrombosis and thrombolysis (2020)
Factor Xa-inhibitor apixaban is an oral anticoagulant prescribed in atrial fibrillation (AF) for stroke prevention. Its pharmacokinetic profile is known to be affected by cytochrome P450 (CYP)3A metabolism, while it is also a substrate of the efflux transporters ATP-binding cassette (ABC)B1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein, BCRP). In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2, ABCB1, CYP3A4*22, CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average 77.2 years old, 85.5 kg, and had a serum creatinine of 103.1 µmol/L. Concomitant amiodarone, an antiarrhythmic agent and moderate CYP3A/ABCB1 inhibitor, the impaired-function variant ABCG2 c.421C > A, and sex predicted higher apixaban concentrations when controlling for age, weight and serum creatinine (multivariate regression; R2 = 0.34). Our findings suggest that amiodarone and ABCG2 genotype contribute to interpatient apixaban variability beyond known clinical factors.
Keyphrases
- atrial fibrillation
- catheter ablation
- left atrial
- oral anticoagulants
- direct oral anticoagulants
- left atrial appendage
- venous thromboembolism
- end stage renal disease
- mass spectrometry
- heart failure
- chronic kidney disease
- ejection fraction
- newly diagnosed
- percutaneous coronary intervention
- healthcare
- high throughput
- prognostic factors
- gene expression
- emergency department
- high resolution
- peritoneal dialysis
- coronary artery disease
- uric acid
- quality improvement
- palliative care
- brain injury
- capillary electrophoresis
- patient reported outcomes
- pain management
- subarachnoid hemorrhage
- health insurance
- weight gain
- cerebral ischemia