Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery.

Détails

ID Serval
serval:BIB_46251D8785FF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery.
Périodique
British journal of clinical pharmacology
Auteur(s)
Kröll D., Stirnimann G., Vogt A., Lai DLL, Borbély Y.M., Altmeier J., Schädelin S., Candinas D., Alberio L., Nett P.C.
ISSN
1365-2125 (Electronic)
ISSN-L
0306-5251
Statut éditorial
Publié
Date de publication
07/2017
Peer-reviewed
Oui
Volume
83
Numéro
7
Pages
1466-1475
Langue
anglais
Notes
Publication types: Clinical Trial, Phase I ; Journal Article
Publication Status: ppublish
Résumé
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 javax.xml.bind.JAXBElement@700c5f48 (coefficient of variation: 10.6), 135.3 μg l javax.xml.bind.JAXBElement@2d9cd44f (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 javax.xml.bind.JAXBElement@156b37e4 (22.3), 136.5 μg l javax.xml.bind.JAXBElement@3f807e6c (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.

Mots-clé
Administration, Oral, Adult, Antithrombins/analysis, Dose-Response Relationship, Drug, Factor Xa Inhibitors/pharmacology, Factor Xa Inhibitors/therapeutic use, Female, Gastric Bypass/adverse effects, Gastric Bypass/methods, Half-Life, Humans, Male, Middle Aged, Obesity/blood, Obesity/surgery, Postoperative Complications/prevention & control, Postoperative Period, Preoperative Period, Prothrombin/analysis, Rivaroxaban/pharmacology, Rivaroxaban/therapeutic use, Thrombin/analysis, Venous Thromboembolism/blood, Venous Thromboembolism/prevention & control, Roux-en-Y gastric bypass, anticoagulation, bariatric surgery, pharmacodynamics, rivaroxaban, sleeve gastrectomy
Pubmed
Web of science
Création de la notice
30/01/2017 19:30
Dernière modification de la notice
12/04/2018 19:23
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