Relative bioavailability of a 5 mg mosapride/10 mg rabeprazole fixed dose combination tablet versus separate single tablets in healthy volunteers: a single-dose randomized open-label crossover study

Abstract

Objective:To evaluate the relative bioavailability of a new formulation containing 5 mg mosapride and 10 mg rabeprazole (T) and compare it with the branded formulations of both drugs co-administered in separate tablets (R) to meet the regulatory requirements of bioequivalence in Argentina.Methods:A randomized-sequence, open-label, two-period crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of either T or R formulations was followed by a 7-day washout period. Blood samples for mosapride were collected before administration (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, and 24 h after administration. Samples for rabeprazole were taken baseline and at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8 and 10 h after dosing. Mosapride and rabeprazole concentrations were determined using a validated LC-MS/MS method. Adverse events were monitored based on clinical parameters and volunteer reports.Results:The geometric means (90% CI) Cmax for mosapride in T and R were 23.13 (20.05–39.45) and 23.09 (21.69–32.37) ng/mL, the AUC0–t were 70.80 (66.23–102.37) and 70.81 (66.35–93.26) ng h/mL and the AUC0–∞ were 74.05 (69.29–106.11) and 74.98 (70.43–97.77) ng h/mL. For rabeprazole T and R the Cmax were 197.42 (186.12–239.91) and 195.50 (186.08–250.07) ng/mL, the AUC0–t were 294.90 (275.13–374.15) and 296.96 (280.11–387.89) ng h/mL and the AUC0–∞ were 301.12 (280.78–380.82) and 304.07 (286.60–394.21), respectively. No differences were detected between the formulations. The T/R ratios (90% CI) for Cmax, AUC0–t and AUC0–∞ were 100.17% (82.35–121.84), 99.99% (87.58–114.16) and 98.77% (87.02–112.11) for mosapride, and 100.99% (85.14–119.77), 99.31% (84.74–116.38) and 99.03% (85.07–115.28) for rabeprazole. No subject complained of adverse events.Conclusions:In this single-dose study, the mosapride/rabeprazole tablets (test formulation) met the criterion for bioequivalence with the reference formulations. Study limitations include single-dose, open-label design, and a small sample of healthy volunteers.