Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor

摘要: BACKGROUND: Apixaban is an oral, selective, direct factor Xa inhibitor approved for thromboprophylaxis after orthopedic surgery and stroke prevention in patients with atrial fibrillation, under development treatment of venous thromboembolism. This study investigated the effect a gastric acid suppressant, famotidine (a histamine H2-receptor antagonist), on pharmacokinetics apixaban healthy subjects. METHODS: two-period, two-treatment crossover randomized 18 subjects to receive single oral dose 10 mg without 40 administered 3 hours before dosing apixaban. Plasma concentrations were measured up 60 post-dose pharmacokinetic parameters calculated. RESULTS: Famotidine did not affect maximum plasma concentration (Cmax) or area concentration-time curve from zero infinite time (AUC∞). Point estimates ratios geometric means close unity Cmax (0.978) AUC∞ (1.007), 90% confidence intervals entirely contained within 80%-125% no-effect interval. Administration alone was well tolerated. CONCLUSION: does apixaban, consistent physicochemical properties (lack ionizable group pH-independent solubility). would be affected by increase gastrointestinal pH due underlying conditions (eg, achlorhydria), pH-mediated effects other antagonists, antacids, proton pump inhibitors. Given that also human organic cation transporter (hOCT), these results indicate are influenced hOCT uptake Overall, support can regard coadministration modifiers.