Titre
Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kröll, D.
Auteure/Auteur
Stirnimann, G.
Auteure/Auteur
Vogt, A.
Auteure/Auteur
Lai, DLL
Auteure/Auteur
Borbély, Y.M.
Auteure/Auteur
Altmeier, J.
Auteure/Auteur
Schädelin, S.
Auteure/Auteur
Candinas, D.
Auteure/Auteur
Alberio, L.
Auteure/Auteur
Nett, P.C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1365-2125
Statut éditorial
Publié
Date de publication
2017-07
Volume
83
Numéro
7
Première page
1466
Dernière page/numéro d’article
1475
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Clinical Trial, Phase I ; Journal Article
Publication Status: ppublish
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.
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.
Sujets
PID Serval
serval:BIB_46251D8785FF
PMID
Date de création
2017-01-30T17:30:17.198Z
Date de création dans IRIS
2025-05-20T18:23:51Z