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 Cmax and AUC0-last, respectively. Food decreased the AUC and Cmax (p < 0.001) and delayed the tmax (p = 0.0077). The investigated women presented higher AUC0-∞ and Cmax 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. .
RCT Entities:
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 Cmax and AUC0-last, respectively. Food decreased the AUC and Cmax (p < 0.001) and delayed the tmax (p = 0.0077). The investigated women presented higher AUC0-∞ and Cmax 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. .
Authors: Dan Atar; Sougat Sarkar; Emil Kolev; Carla Mura; Frank Brosstad; Lotte Theodorsen; Geir Ivar Westen; Per Erik Stribolt-Halvorsen Journal: Int J Clin Pharmacol Ther Date: 2022-10 Impact factor: 0.976