Study of bioequivalence between two formulations containing dipyrone 300 mg + isometheptene mucate 30 mg + caffeine 30 mg: a randomized, open-lable, two period crossover study in healthy adult Brazilian volunteers/ Bioequivalência entre duas formulações contendo 300 mg de dipirona + 30 mg de mucato de isometepteno + cafeína 30 mg: um estudo cruzado randomizado, aberto e de dois períodos, em voluntários brasileiros adultos saudáveis

Alessandra Ferreira dos Santos, Quevellin Alves dos Santos Francisco, Carlos Eduardo Melo Correa, Vanessa Bergamin Boralli Marques

Abstract


The combination of dipyrone 300 mg, isometheptene mucate 30 mg and caffeine 30 mg in a single tablet is widely used in Brazil for the acute treatment of various forms of primary headaches. This study aimed to evaluate the bioequivalence between two formulations containing the combination of these active ingredients. An open-label, randomized, single-dose, two-period, two-sequence, two-treatment crossover study was conducted in 80 healthy subjects of both genders. Subjects received a single dose of test coated tablet (Sedamed®, Cimed Indústria de Medicamentos Ltda.) and reference product (Neosaldina®, Nycomed Pharma Ltda.) under fasting conditions according to a randomly assigned order with a 7-day washout period. Serial blood samples were collected up to 24h post-dose. Plasma concentrations of active pharmaceutical ingredients were obtained by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated using non-compartmental methods. There were no serious adverse events during the study and both formulations were safe and well tolerated during the study. Geometric mean ratios (90% confidence intervals) for Cmax and AUC0-t were 97.04% (94.94 – 99.19) and 98.77% (95.58 – 102.06) for 4-MAA and 100.12% (93.33 – 107.41) and 96.19% (91.24 – 101.42) for isometheptene, respectively. The test formulation of was considered bioequivalent to reference product according to regulatory requirements, and therefore interchangeable.


Keywords


Bioequivalence, dipyrone, 4-methylaminoantipyrine, isometheptene, LC-MS/MS.

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References


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DOI: https://doi.org/10.34117/bjdv6n1-336

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