Journal Article

Effect of Activated Charcoal on Rivaroxaban Complex Absorption

Mismetti, Patrick, De Magalhaes, Elodie, Bertoletti, Laurent, Ollier, Edouard, Accassat, Sandrine, Lanoiselée, Julien, Delavenne, Xavier, Escal, Jean, Hodin, Sophie, Basset, Thierry

2017

Overview

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.

• Publisher: Springer International Publishing,Springer Nature B.V,Springer Verlag
• Subject: Adult / Anticoagulants / Bioavailability / Charcoal / Charcoal - administration & dosage / Charcoal - pharmacology / Cross-Over Studies / Cytochrome / Drug Administration Schedule / Drug dosages / Drug Overdose - drug therapy / Factor Xa Inhibitors - blood / Factor Xa Inhibitors - pharmacokinetics / Glycoproteins / Humans / Internal Medicine / Intestinal Absorption / Laboratories / Life Sciences / Male / Medicine / Medicine & Public Health / Models, Biological / Original Research Article / Pharmaceutical sciences / Pharmacology/Toxicology / Pharmacotherapy / Population / Proteins / Rivaroxaban - blood / Rivaroxaban - pharmacokinetics / Thromboembolism / Young Adult