Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in health

Authors

  • Alessandra Ferreira dos Santos Instituto Claudia Marques de Pesquisa e Desenvolvimento Ltda. https://orcid.org/0000-0002-5620-8535
  • Quevellin Alves dos Santos Instituto Claudia Marques de Pesquisa e Desenvolvimento Ltda.
  • Carlos Eduardo Melo Correa Instituto Claudia Marques de Pesquisa e Desenvolvimento Ltda.
  • Edvaldo Capobiango Coelho Instituto Claudia Marques de Pesquisa e Desenvolvimento Ltda.

DOI:

https://doi.org/10.1590/s2175-97902020000217836

Keywords:

Acetaminophen, Phenylephrine, Chlorpheniramine, Bioequivalence, Partially replicated crossover, Ultra-high performance liquid chromatography, Mass spectrometry

Abstract

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable.

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Published

2020-12-09

How to Cite

Santos, A. F. dos ., Santos, Q. A. dos ., Correa, C. E. M. ., & Coelho, E. C. . (2020). Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in health. Brazilian Journal of Pharmaceutical Sciences, 56, e17836 . https://doi.org/10.1590/s2175-97902020000217836

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