ABSTRACT
The bioequivalence (BE) of orally administered capsules versus film tablets containing 20 and 10 mg of rivaroxaban was assessed in 2 single-dose, open-label, randomized 2-way crossover trials with a washout period of at least 1 week. The study for the 10 mg strength was conducted under fasting conditions (n = 68) and the study for the 20 mg strength under fed conditions (n = 52). Blood samples were collected over a 36-hour period and concentrations were assayed using a liquid chromatography tandem mass spectrometry method. Pharmacokinetic (PK) evaluation was performed with the program Phoenix WinNonlin, for non-compartmental assessment of data. After administration of 10 mg rivaroxaban under fasting conditions, mean Area Under the time - concentration Curve until the last blood sampling point (AUCt ), Area Under the time - concentration Curve until infinity (AUC∞ ), and maximum plasma concentration (Cmax ) were comparable (972 ng/mL*h, 1048 ng/mL*h, and 111 ng/mL, respectively, for the test and 1013 ng/mL*h, 1070 ng/mL*h and 130 ng/mL, respectively, for the reference formulation). Mean AUCt , AUC∞ , and Cmax were also comparable under fed conditions after administration of 20 mg rivaroxaban (2145 ng/mL*h, 2198 ng/mL*h and 275 ng/mL, respectively, for the test and 1856 ng/mL*h, 1916 ng/mL*h and 240 ng/mL, respectively, for the reference formulation). The 90% confidence intervals for all PK parameters were within the acceptance range of 80%-125%, suggesting BE between the generic product and the innovator product in healthy Caucasian male subjects. A clinically relevant difference in the tolerability and safety of the treatments was not detected. Study results indicated that the capsule formulations were bioequivalent with the film tablet formulations.
