Abstract

Objective: To perform a comparative bioavailability study between a test (re-formulation) and a reference acetylsalicylic acid formulation (Ecasil-81, 81 mg coated tablet) in healthy subjects under fed condition.
Materials and methods: Healthy subjects (n = 48) were included in this monocentric, open-label, randomized, two-way crossover pharmacokinetic study. They received a single 81-mg oral dose of a test or a reference formulation of acetylsalicylic acid under fed condition, with a 7-day washout period between the treatments. Blood samples were collected over a period of 36 hours. The salicylic acid plasma concentration was measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Pharmacokinetic analysis was performed using WinNonlin software.
Results: The geometric mean and 90% confidence interval of test/reference formulation ratios were 109.32% (102.54 – 116.54%) and 106.94% (102.97 – 111.07%) for salicylic acid C_max and AUC_0–last, respectively. Food decreased the AUC and C_max (p < 0.001) and delayed the t_max (p = 0.0077). The investigated women presented higher AUC_0–∞ and C_max values (p < 0.001) than men. The clinical and laboratory exams did not show significant alterations.
Conclusion: The re-formulation is bioequivalent to the reference formulation regarding the absorption extent and rate in fed healthy subjects. The administration of acetylsalicylic acid with food decreased its bioavailability. Moreover, differences in salicylic acid disposition related to sex were observed. The treatments were well tolerated by the investigated subjects.

Author Details

Authors

• Raul Cleverson Dolores¹
• Natalícia de Jesus Antunes¹
• Alexandre Scremin Czezacki²
• Carolina Previato²
• Rafael Campos^{1, 3}
• Ronilson A. Moreno⁴
• Gustavo D. Mendes^{2, 5}
• Gilberto De Nucci^{1, 2, 5}

Departments

• ¹ Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP),
• ² Department of Pharmacology, Faculty of Medicine, São Leopoldo Mandic, Campinas, SP,
• ³ Superior Institute of Biomedical Sciences, Ceará State University (UECE), Fortaleza, Ceará,
• ⁴ Department of Food Science, School of Food Engineering, UNICAMP, Campinas, and
• ⁵ Department of Pharmacology, Faculty of Medicine, Metropolitan University of Santos, Santos, SP, Brazil

Address

Natalícia de Jesus Antunes, PhD

State University of Campinas (UNICAMP)
Faculty of Medical Sciences
Department of Pharmacology
Alexander Fleming St, 105
13083-881, Campinas, SP, Brazil
Email: [email protected]

Citation