Pharmacokinetics and pharmacodynamics of single doses of Rivaroxaban in obese patients before and after bariatric surgery.

Kröll, Dino; Stirnimann, Guido; Vogt, Andreas; Lai, Desirée Lin Lee; Borbély, Yves Michael; Altmeier, Julia; Schädelin, Sabine; Candinas, Daniel; Alberio, Lorenzo; Nett, Philipp C. (2017). Pharmacokinetics and pharmacodynamics of single doses of Rivaroxaban in obese patients before and after bariatric surgery. British journal of clinical pharmacology, 83(7), pp. 1466-1475. Wiley-Blackwell 10.1111/bcp.13243

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AIMS 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. METHODS In this single-centre study, obese patients received single oral doses of rivaroxaban (10 mg) one day before and three days after bariatric surgery. PK and PD parameters were assessed at baseline and during 24 hours after drug ingestion. RESULTS Six Roux-en-Y Gastric bypass patients (RYGB) and 6 Sleeve gastrectomy (SG) patients completed the study. Mean rivaroxaban AUC, Cmax , tmax and T1/2 were 971.9 µg · h/L (coefficient of variation: 10.6) , 135.3 µg/L (26.7), 1.5 h and 13.1 h (34.1) before and 1165.8 (10.6), 170.0 (26.7), 1.5 and 8.9 (34.1) post-surgery for SG patients and 933.7 µg · h/L (22.3), 136.5 µg/L (10.7), 1.5 h und 13.8 h (46.6) before and 1029.4 (22.3), 110.8 (10.7), 2.5 and 15 (46.6) post-surgery for RYGB patients, respectively. Prothrombin fragments (F1 + 2) decreased during the first 12 hours and increased thereafter in the pre- and the post-bariatric setting. Thrombin-antithrombin complexes dropped within one to three hours in the pre-bariatric setting and remained low after surgery until they increased at 24 hours post-dose. Rivaroxaban was well tolerated and no relevant safety issues were observed. CONCLUSIONS Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic post-bariatric anticoagulation is supported by changes in PD.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy

UniBE Contributor:

Kröll, Dino; Stirnimann, Guido; Vogt, Andreas; Borbély, Yves Michael; Altmeier, Julia; Candinas, Daniel and Nett, Philipp C.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0306-5251

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Jeannie Wurz

Date Deposited:

09 May 2017 16:07

Last Modified:

10 Mar 2018 02:30

Publisher DOI:

10.1111/bcp.13243

PubMed ID:

28121368

Uncontrolled Keywords:

Roux-en-Y gastric bypass; anticoagulation; bariatric surgery; pharmacodynamics; rivaroxaban; sleeve gastrectomy

BORIS DOI:

10.7892/boris.96449

URI:

https://boris.unibe.ch/id/eprint/96449

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