Relative bioavailability and pharmacokinetic comparison of a fixed-dose combination tablet of mosapride, pancreatin, and simethicone relative to single-component mosapride tablets in healthy Mexican subjects

Abbott Laboratories de Mexico S.A. de C.V. developed a new fixed-dose combination of mosapride 5 mg, pancreatin 170 mg, and simethicone 125 mg as an alternative to the mosapride monotherapy to improve overall satisfaction and adequate relief of gastrointestinal disorders symptoms and to reduce multiple pill burden. As a part of the fixed-dose combination registration process in Mexico, a pharmacokinetic and relative bioavailability study was carried out to demonstrate nonexistence of pharmacokinetic interaction when mosapride is administered alone or in combination with pancreatin and simethicone using DOSIER (R) (mosapride) 5-mg tablets as a reference product. Tolerability of the fixed-dose combination tablet was assessed. In this open-label, randomized, oral single-dose, two-way crossover study, 65 healthy male and female subjects received either the fixed-dose combination tablet or the reference product during each study period. The two study periods were separated by a 7-day washout period. Mosapride concentrations in plasma samples were determined using a validated ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method. Blood samples were collected for up to 16 h post dose. The primary evaluation criteria were C-max and AUC(0-t) for mosapride. The 90% confidence intervals for the ratio of geometric means for C-max (96.12% to 110.90%) and AUC(0-t) (99.07% to 108.06%) were within the defined acceptance limits of 75% to 133% and 80% to 125% for C-max and AUC(0-t), respectively, indicating bioequivalence between the two products. Both products were safe and well tolerated. Therefore, mosapride in combination with pancreatin and simethicone tablet is bioequivalent to mosapride alone, and no new safety signals emerged.