RESUMO
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.
