Estudo de bioequivalencia entre duas formulações farmaceuticas (comprimidos) contendo 20mg de Lisinopril, em voluntarios sadios de ambos os sexos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

The aim of this study was to evaluate the bioequivalence between two formulations of lisinopril 20 mg. The test formulation was Lisinopril tablet 20 mg, manufactured by Medley S/A Indústria Farmacêutica (Iot # LlC 06/01-1; expiry date: june/03) and the reference formulation was Zestril@ tablet 20 mg, manufactured by Astra Zeneca (Iot # A03534; expiry date: october/04). The bioequivalence study design was an open, randomized, two-period crossover (2-sequence), with a 2-week washout interval, in 26 healthy volunteers, both sexes (balanced), single dose (20 mg), in fasting conditions. The blood samples collecting were O, 1 h, 2h, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min,6h, 6h30min, 7h, 7h30min, 8h, 8h30min, 9h, 10h, 12h, 24h e 48h. The total plasma concentrations were quantified by a validated method, using high-performance liquid chromatography coupled to mass spectrometry (LC-M5-MS), with electrospray ionization running in positive mode (ES+) and Multiple Reaction Monitoring (MRM). The limit of quantification (LOQ) was 2 ng/ml.The precision and accuracy, calculed from LOQ samples (n=8) were 8.9 % and 98.9 % respectivetely. The method had a chromatographic total run time of 6.5 mino and was linear within the range 2.00 - 200 nglml. The mean recoveries observed (n=5) for lisinopril were 79.2:t 5.9 %,80.3:t 3.4 % and 82.5:t 3.9 % (3.00, 30.0 and 150 ng/ml, respectively). The mean recoveries observed (n=5) for enalaprilat were 77.7 :t 7.2 %. From the log-transformation of the plasma concentrations values were obtained the pharmacokinetics parameteres for the bioequivalence calculation: Cmax (absorption rate) and AUCo-t (absorption extension). It was evaluated by ANOVA the effects of period, sequence, product and subject in the sequence for Cmax and AUCo-t. Only the subject in the sequence was considered statistically significant, showing the presence of significative interindividual variability. The 90 % confidence interval was based on the residual variance of ANOVA. The geometric mean and the 90 % CI testlreference ratios were 95.5 % (85.0 - 107.4 %) for AUC Iast and 92.6 % (81.7 - 105.1 %) for Cmax. Since the 90 % CI for for AUCIast and Cmax ratios are within the 80-125 % interval proposed by the ANVISA, it concludes that Lisinopril 20 mg tablet (test formulation) is bioequivalent to Zestril@ 20 mg tablet, in terms of both rate and extent of absorption

ASSUNTO(S)

enalaprilo farmacocinetica biodisponibilidade

ACESSO AO ARTIGO

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