Abstrait

An In Vitro Analysis of the Effects of Phosphate Binders on the Dissolution Profile of Rivaroxaban Tablets

Ponniah Shenbagamurthi, William Heffner, David P Thomas and Mark A Krook

The Objective: Clinical trials are evaluating the use of rivaroxaban in patients with end-stage renal disease (ESRD), including those taking phosphate binders. The purpose of this in vitro dissolution study was to assess the potential for interactions between rivaroxaban and phosphate binders.

Methods: Two phosphate binders, calcium acetate (667 mg) and sevelamer carbonate (800 mg), were evaluated for their effects on the dissolution of rivaroxaban tablets (15 mg). Dissolution profiles were analyzed as the percent of label claim rivaroxaban over 120 minutes. Similarity factor (f2) calculations were used to compare dissolution profiles between rivaroxaban alone and rivaroxaban in combination with calcium acetate or sevelamer carbonate.

Results: In water (1800 mL), neither calcium acetate nor sevelamer carbonate inhibited dissolution of rivaroxaban. The mean percentage of dissolved rivaroxaban increased across all three experiments, ranging from 61% to 67% at 10 minutes to 89% to 92% at 120 minutes. Values for f2 were 64.1 for rivaroxaban plus calcium acetate and 84.5 for rivaroxaban plus sevelamer carbonate, indicating that the dissolution profiles were similar.

Conclusion: The phosphate binders did not bind or interact with rivaroxaban in vitro; thus, no change in efficacy would be expected for patients with ESRD receiving either of these products in combination with rivaroxaban.