Pharmacodynamics and Pharmacokinetics of oral factor Xa inhibitors

Abstract

Pontus B Persson Institute of Vegetative Physiology, Berlin, GermanyApixaban and rivaroxaban are oral factor Xa inhibitors. In a recent issue of Clinical Pharmacology: Advances and Applications, Frost et al compare apixaban (2.5 mg, twice daily) to rivaroxaban (10 mg, once daily) with regard to their pharmacokinetics and pharmacodynamics.1 Both oral factor Xa inhibitors have similar half-lives. Moreover, as may seem intuitive, the twice daily regime of apixaban revealed a less pronounced peak-to-trough plasma concentration ratio than rivaroxaban which is given once daily. The latter finding lead the authors to suggest a more constant anticoagulant effect of twice-daily apixaban, when compared to the once daily dose of rivaroxaban.Suggesting more constant anticoagulation by the twice-daily apixaban regimen is premature due to the author’s disregard of a crucial pharmacokinetic feature: drug accumulation. Apixaban may have accumulated during the twice-daily regimen, as indicated by the increasing trough values (see values for 12h and 24h in Figure 2 of that study). That Figure claims to show data at steady state, however, trough values rise, indicating drug accumulation after a time period, when a steady state is usually reached (5 half-lives). Uncontrolled accumulation cannot be ruled out.View original paper by Frost and colleagues.