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Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects
Author(s) -
Upreti Vijay V.,
Wang Jessie,
Barrett Yu Chen,
Byon Wonkyung,
Boyd Rebecca A.,
Pursley Janice,
LaCreta Frank P.,
Frost Charles E.
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12114
Subject(s) - apixaban , medicine , pharmacokinetics , tolerability , cmax , pharmacodynamics , adverse effect , pharmacology , anesthesia , atrial fibrillation , rivaroxaban , warfarin
Aim Apixaban is an oral, direct, factor‐ X a 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 X a 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 ( C max ) 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 C max and AUC (0,∞) , respectively. Apixaban renal clearance was similar across the weight groups. Plasma anti‐factor X a 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.