Abstract
Objective
To quantify the impact of activated charcoal (AC) on rivaroxaban exposure in healthy volunteers.
Methods
This was an open-label study with an incomplete cross-over design of single-dose rivaroxaban (40 mg) administered alone or with AC in 12 healthy volunteers. The study comprised three treatment periods in randomised sequence, one with rivaroxaban administered alone and two with AC given at 2, 5 or 8 h post-dose. Rivaroxaban plasma concentration was measured in blood samples drawn at 16 time points. The pharmacokinetic model of rivaroxaban alone or with AC administration was built using a non-linear mixed-effect modelling approach.
Results
The pharmacokinetic model was based on a one-compartment model with an absorption rate described by the sum of three inverse Gaussian densities to reproduce multiphasic and prolonged absorption. The inclusion in the model of each AC administration schedule significantly improved objective function value. AC reduced the area under the rivaroxaban concentration-time curve by 43% when administered 2 h post-dose, by 31% when administered 5 h post-dose and by 29% when administered 8 h post-dose. Based on the estimated pharmacokinetic model, simulations suggested that AC might have an impact even after 8 h post-dose.
Conclusion
AC administration significantly reduces exposure to rivaroxaban even if AC is administered 8 h after rivaroxaban. These results suggest that AC could be used in rivaroxaban overdose and accidental ingestion to antagonise absorption.
ClinicalTrial.gov registration no.
NCT02657512.
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This research has received funding support from the University Hospital of Saint-Etienne, and was sponsored by the University Hospital of Saint-Etienne.
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Edouard Ollier, Sophie Hodin, Julien Lanoisele, Jean Escal, Sandrine Accassat, Elodie De Magalhaes, Thierry Basset, Laurent Bertoletti, Patrick Mismetti and Xavier Delavenne declare that they have no conflicts of interest that are directly relevant to the content of this article
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Ollier, E., Hodin, S., Lanoiselée, J. et al. Effect of Activated Charcoal on Rivaroxaban Complex Absorption. Clin Pharmacokinet 56, 793–801 (2017). https://doi.org/10.1007/s40262-016-0485-1
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DOI: https://doi.org/10.1007/s40262-016-0485-1