title: Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery.
abstract: Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery. Studies of direct oral anticoagulants (DOACs) are not available in this surgical field. The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic (PK/PD) parameters of rivaroxaban in bariatric patients.
  
  
  
  In this single-centre study, obese patients received single oral doses of rivaroxaban (10 mg) 1 day prior to and 3 days after bariatric surgery. PK and PD parameters were assessed at baseline and during 24 h after drug ingestion.
  
  
  
  Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study. Mean rivaroxaban area under plasma concentration-time curve, peak plasma concentration, time to peak plasma concentration and terminal half-life were 971.9 μg·h l-1(coefficient of variation: 10.6), 135.3 μg l-1(26.7), 1.5 h and 13.1 h (34.1) prior to and 1165.8 (21.9), 170.0 (15.9), 1.5 and 8.9 (44.6) postsurgery for SG patients and 933.7 μg·h l-1(22.3), 136.5 μg l-1(10.7), 1.5 h und 13.8 h (46.6) prior to and 1029.4 (7.4), 110.8 (31.8), 2.5 and 15 (60.0) postsurgery for Roux-en-Y gastric bypass patients, respectively. Prothrombin fragments (F1 + 2) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting. Thrombin-antithrombin complexes dropped within 1-3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose. Rivaroxaban was well tolerated and no relevant safety issues were observed.
  
  
  
  Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in PD.
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Dino
authors.initials: D
authors.lastname: Kröll
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Guido
authors.initials: G
authors.lastname: Stirnimann
authors.affiliation: Department of Anaesthesiology, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vogt
authors.affiliation: Department of Anaesthesiology, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Desirée Lin Lee
authors.initials: DLL
authors.lastname: Lai
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Yves Michael
authors.initials: YM
authors.lastname: Borbély
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Altmeier
authors.affiliation: Department of Clinical Research, Clinical Trial Unit, Spitalstrasse 12, 4031, Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schädelin
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Candinas
authors.affiliation: Division of Haematology and Central Haematology Laboratory, Centre Hospitalier Universitaire Vaudois, University of Lausanne, CH 1011, Lausanne, Switzerland.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Alberio
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Philipp C
authors.initials: PC
authors.lastname: Nett
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000991:Antithrombins / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects* / Q000379:methods; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000601:surgery*; D011183:Postoperative Complications / Q000517:prevention & control*; D011184:Postoperative Period; D057234:Preoperative Period; D011516:Prothrombin / Q000032:analysis; D000069552:Rivaroxaban / Q000494:pharmacology* / Q000627:therapeutic use; D013917:Thrombin / Q000032:analysis; D054556:Venous Thromboembolism / Q000097:blood / Q000517:prevention & control*
chemical_list: D000991:Antithrombins; D065427:Factor Xa Inhibitors; D011516:Prothrombin; D000069552:Rivaroxaban; D013917:Thrombin
keywords: Roux-en-Y gastric bypass; anticoagulation; bariatric surgery; pharmacodynamics; rivaroxaban; sleeve gastrectomy