RESUMEN
Abbott Laboratories de México 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® (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 Cmax and AUC0-t for mosapride. The 90% confidence intervals for the ratio of geometric means for Cmax (96.12% to 110.90%) and AUC0-t (99.07% to 108.06%) were within the defined acceptance limits of 75% to 133% and 80% to 125% for Cmax and AUC0-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.
Asunto(s)
Pancreatina , Simeticona , Área Bajo la Curva , Benzamidas , Disponibilidad Biológica , Cromatografía Liquida , Estudios Cruzados , Femenino , Humanos , Masculino , México , Morfolinas , Comprimidos , Espectrometría de Masas en Tándem , Equivalencia TerapéuticaRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive rise in pulmonary vascular resistance. Ambrisentan is an oral, propanoic acid based-endothelin receptor antagonist (ERA), selective for the endothelin type-A receptor, which is approved for the treatment of PAH. The Colombia National Food and Drug Surveillance Institute regulatory criteria require demonstrating that the proposed generic product is bioequivalent to its reference-listed drug to obtain marketing approval. OBJECTIVES: The purpose of this study was to test the bioequivalence, pharmacokinetics, and tolerability of ambrisentan 10 mg tablets. METHODS: In this open-label, randomized, oral single-dose, two-way crossover bioequivalence study, 26 Mexican adult healthy male subjects received either the generic product of ambrisentan 10 mg or the reference product Volibris® (ambrisentan) 10 mg tablets during each study period under fasting conditions. There was a 7-day washout period between each dosing. Ambrisentan concentrations in plasma samples were quantified using a validated ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method. Blood samples were collected up to 72 h post-dose in each study period. The primary end points were maximum plasma concentration (Cmax) and area under the plasma concentration-time (AUC0-t) curve between 0 and 72 h for ambrisentan. RESULTS: The ratios (90% CI) of geometric mean for ambrisentan were 104.3% (97.12-111.98%) and 100.2% (95.56-104.72%). These pharmacokinetic parameter values lie within the INVIMA-specified bioequivalence limits of 80%-125%. Nervous system disorders were the most common adverse events (AEs). All AEs were mild to moderate in nature and were resolved after follow-up or pharmacologic treatment. Both products were safe and well tolerated. CONCLUSIONS: The test product ambrisentan 10 mg tablets is bioequivalent to the reference product Volibris® (ambrisentan) 10 mg tablets. Both treatments were well tolerated in the Mexican male population of this study. TRIAL REGISTRATION: COFEPRIS National Clinical Trials Registry number 183300410B0367/2018.