Estudo de farmacocinetica comparativa de uma formulação de amlodipina + maleato de enalapril versus uma formulação de amlodipina e versus uma formulação de maleato de enalapril em voluntarios sadios de ambos os sexos / Comparative pharmacokinetics study of a formulation of amlodipine + enalapril versus an enalapril maleate formulation in healthy volunteers of both genders




Introduction: Based on evidence of studies showing that in 2/3 of the cases of hypertension monotherapy is not enough to reach pressure reduction and facing the necessity of a more rigorous control, there is a clear current trend to the early introduction of a combined therapy of anti-hypertensive drugs as first pharmacological measure. These associations of anti-hypertensives can be made through separate products or through associations in fixed doses. Among the known efficient associations there is the case of angiotensin converting enzyme (ACE) inhibitors and calcium channels blockers; an example of these associations is the one of amlodipine and enalapril. Objective: This study analyses the comparative pharmacokinetics of a product containing amlodipine, a second one containing enalapril against a product containing the two active principles. The product test, Sinergenè (5mg/20mg) was manufactured by Laborat?ios Biosint?ica Ltda. The reference product for Amlodipina was Norvascè, 5 mg tablet, manufactured by Laborat?io Pfizer Ltda and the reference product for Enalapril was Renitecè, 20 mg tablet, manufactured by Merck Sharp Dohme. Materials and methods: 36 healthy volunteers of both genders were confined in three periods during which they received the association of amlodipina and enalapril, amlodipine individually and enalapril individually. Collects at regular intervals during 144 hours for amlodipine and 24 hours for enalapril were measured through a proper validated analytical method. The plasmatic concentrations of Amlodipine, Enalapril and enalaprilate were measured by a proper validated analytical method of mass spectrometry (LC-MS-MS). The statistical analysis was performed by ANOVA. Results: The relation of test and reference of the formulations for the parameters Cmax and AUC were within 80-125%. Conclusion: After statistical analysis by ANOVA, we reached the conclusion that the test formulation, Sinergen, is bioequivalent to the reference formulations Renitec (Enalapril) and Novarsec (amlodipina), since all the T/R relations for Cmax, AUC 0-inf and AUC 0-last of the formulations were within 80%-125% interval determined by ANVISA as condition of bioequivalence


bioequivalencia bioequivalence mass spectrometry enalapril pharmacokinetics espectrometria de massa farmacocinetica amlodipina amlodipine enalapril

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