Extremes of body weight altered apixaban exposure, with low weight (≤50 kg) showing 27% higher Cmax (90% CI 8-51%) and high weight (≥120 kg) showing 31% lower Cmax compared to reference.
Observational (n=54)
Open-label
Do extremes of body weight affect the pharmacokinetics, pharmacodynamics, and safety of a single 10 mg oral dose of apixaban in healthy subjects?
Extremes of body weight result in modest changes in apixaban exposure that are unlikely to require dose adjustment based on body weight alone.
AIM: Apixaban is an oral, direct, factor-Xa inhibitor approved for thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. This open label, parallel group study investigated effects of extremes of body weight on apixaban pharmacokinetics, pharmacodynamics, safety and tolerability. METHOD: Fifty-four healthy subjects were enrolled 18 each into low (≤50 kg), reference (65-85 kg) and high (≥120 kg) body weight groups. Following administration of a single oral dose of 10 mg apixaban, plasma and urine samples were collected for determination of apixaban pharmacokinetics and anti-factor Xa activity. Adverse events, vital signs and laboratory assessments were monitored. RESULTS: Compared with the reference body weight group, low body weight had approximately 27% 90% confidence interval (CI): 8-51% and 20% (90% CI: 11-42%) higher apixaban maximum observed plasma concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUC(0,∞)), respectively, and high body weight had approximately 31% (90% CI: 18-41%) and 23% (90% CI: 9-35%) lower apixaban Cmax and AUC(0,∞) , respectively. Apixaban renal clearance was similar across the weight groups. Plasma anti-factor Xa activity showed a direct, linear relationship with apixaban plasma concentration, regardless of body weight group. Apixaban was well tolerated in this study. CONCLUSION: The modest change in apixaban exposure is unlikely to require dose adjustment for apixaban based on body weight alone. However, caution is warranted in the presence of additional factors (such as severe renal impairment) that could increase apixaban exposure.
Upreti et al. (2013) conducted an observational in Healthy subjects (n=54). Apixaban vs. Reference body weight group (65-85 kg) was evaluated on Apixaban maximum observed plasma concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUC(0,∞)). Extremes of body weight altered apixaban exposure, with low weight (≤50 kg) showing 27% higher Cmax (90% CI 8-51%) and high weight (≥120 kg) showing 31% lower Cmax compared to reference.