title: Effect of Activated Charcoal on Rivaroxaban Complex Absorption.
abstract: To quantify the impact of activated charcoal (AC) on rivaroxaban exposure in healthy volunteers.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  NCT02657512.
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France. ed.ollier@gmail.com.|Laboratoire de Pharmacologie Toxicologie, INSERM UMR1059, CHU de Saint-Etienne, Hôpital Nord, 42055, Saint-Étienne, France. ed.ollier@gmail.com.|Université Claude Bernard Lyon 1, Villeurbanne, France. ed.ollier@gmail.com.
authors.forename: Edouard
authors.initials: E
authors.lastname: Ollier
authors.affiliation: Laboratoire de Pharmacologie Toxicologie, INSERM UMR1059, CHU de Saint-Etienne, Hôpital Nord, 42055, Saint-Étienne, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hodin
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France.|Laboratoire de Pharmacologie Toxicologie, INSERM UMR1059, CHU de Saint-Etienne, Hôpital Nord, 42055, Saint-Étienne, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lanoiselée
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France.|Laboratoire de Pharmacologie Toxicologie, INSERM UMR1059, CHU de Saint-Etienne, Hôpital Nord, 42055, Saint-Étienne, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Escal
authors.affiliation: Laboratoire de Pharmacologie Toxicologie, INSERM UMR1059, CHU de Saint-Etienne, Hôpital Nord, 42055, Saint-Étienne, France.|Université Jean Monnet, Université de Lyon, Saint-Étienne, France.|Unité de Recherche Clinique Innovation et Pharmacologie, CHU de Saint-Etienne, Saint-Étienne, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Accassat
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France.|Service de Médecine Thérapeutique, CHU de Saint-Etienne, Saint-Étienne, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: De Magalhaes
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France.|Laboratoire de Pharmacologie Toxicologie, INSERM UMR1059, CHU de Saint-Etienne, Hôpital Nord, 42055, Saint-Étienne, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Basset
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France.|Service de Médecine Thérapeutique, CHU de Saint-Etienne, Saint-Étienne, France.|Université Jean Monnet, Université de Lyon, Saint-Étienne, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bertoletti
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France.|Service de Médecine Thérapeutique, CHU de Saint-Etienne, Saint-Étienne, France.|Université Jean Monnet, Université de Lyon, Saint-Étienne, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.affiliation: INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France.|Laboratoire de Pharmacologie Toxicologie, INSERM UMR1059, CHU de Saint-Etienne, Hôpital Nord, 42055, Saint-Étienne, France.|Université Jean Monnet, Université de Lyon, Saint-Étienne, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Delavenne
mesh_terms: D000328:Adult; D002606:Charcoal / Q000008:administration & dosage* / Q000494:pharmacology; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000188:drug therapy; D065427:Factor Xa Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D000069552:Rivaroxaban / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D065427:Factor Xa Inhibitors; D002606:Charcoal; D000069552:Rivaroxaban