Bioequivalence and Tolerability of Ambrisentan: A Pharmacokinetic Study in Mexican Healthy Male Subjects
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ORIGINAL RESEARCH ARTICLE
Bioequivalence and Tolerability of Ambrisentan: A Pharmacokinetic Study in Mexican Healthy Male Subjects Karen Paola Camarillo Cárdenas1 · Joceline Estefanía Rangel Velázquez1 · Javier Jesús Osorio Escobar1 · Juan Chirinos2 · Murali Pendela1
© Springer Nature Switzerland AG 2020
Abstract 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
* Karen Paola Camarillo Cárdenas [email protected] 1
Avant Santé Research Center S.A. de C.V, San Pedro Garza García, Nuevo León, México
Abbott Laboratories de Colombia, Bogotá, Colombia
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Vol.:(0123456789)
K. P. C. Cárdenas et al.
Key Points The oral administration of ambrisentan 10 mg tablets is bioequivalent to the reference product Volibris® (ambrisentan) 10 mg. No tolerability problems were observed with either product. There are no interracial differences in pharmacokinetics of ambrisentan. The findings of this study will help to under
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