Full Dose Rivaroxaban in Patients with a History of Bariatric Surgery: Bridging the Knowledge Gap through a Phase 1 Study.

ABSTRACT

BACKGROUND: Bariatric surgery (BS) induces significant changes in gastrointestinal anatomy, potentially influencing the pharmacokinetics of orally administered drugs such as rivaroxaban. OBJECTIVES: This Phase 1 study aimed to assess the pharmacokinetics and safety of full-dose rivaroxaban in post-BS patients. METHODS: The ABSORB study was a single-center, non-randomized, multiple-dose, parallel-design bioequivalence trial. Adult patients with stable weight post Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were compared with subjects with class III obesity and healthy controls. Participants received 20 mg of rivaroxaban daily for 8 days. RESULTS: Post-BS patients exhibited altered rivaroxaban pharmacokinetics, suggesting reduced absorption. Mean AUC0-24h (area under the concentration-time curve from time 0 to 24 hours) after the first dose (RYGB 1806.8 ng.h/mL; SG 1648.9 ng.h/mL) was lower compared to controls (1893.5 ng.h/mL). At steady-state (AUCss), AUC values remained lower in BS groups (RYGB 2129.9 ng.h/mL; SG 1946.4 ng.h/mL) than controls (2224.8 ng.h/mL). The maximum concentration after the first dose was lower in post-RYGB subjects (214.9 ng/mL) than controls (264.1 ng/mL). This difference was less pronounced at steady-state (RYGB 256.9 ng/mL vs. controls 288.8 ng/mL). Neither BS group met bioequivalence criteria compared to controls, whereas the group with class III obesity met bioequivalence criteria compared to controls at steady state. CONCLUSION: Rivaroxaban displayed minor pharmacokinetic variations in post-BS patients. Given reported inter-individual variability in the general population, these variations are unlikely to be of clinical significance. Our findings support rivaroxaban use in BS patients, emphasizing the need for further research in this area.