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.
