ABSTRACT
Introduction: Montelukast, a selective and active leukotriene receptor antagonist, is one of the most common agents in asthma treatment for both adults and children. Objective: To assess whether the pharmacokinetic profiles of two formulations of montelukast were similar after a single 5 mg dose (chewable tablets), administered orally under fasting conditions, sampling blood before and 36 hours after administration. Methods: This was a randomized, 2-sequence, 2-period, crossover study of 2 chewable tablet formulations of the drug: Singulair®, provided by Merck Sharp and Dohme Farmacêutica Ltda. (reference), and generic montelukast, manufactured by Eurofarma Laboratórios S.A. (test). Plasma samples obtained from 35 participants were analyzed for montelukast through high-performance liquid chromatography coupled to tandem mass spectrometry, with montelukast-d6 as the internal standard. Peak montelukast concentrations were 299.313 (SD, 11.039) ng/mL for the reference formulation and 279.803 (SD, 10.085) ng/mL for test formulation. Results: Statistical analysis showed no significant differences between AUC0-36h, AUC0-inf, or Cmax between formulations, with the following test/reference ratios: 102.458 for AUC0-36h, 102.522 for AUC0-inf, and 93.490 for Cmax. No serious adverse events were reported during the trial. Our results demonstrated the bioequivalence of Singulair® and Eurofarma's generic montelukast. Conclusions: Our results revealed that the new generic tablets are clinically safe and can be used interchangeably with the brand name product. Eurofarma's montelukast offers a safe, effective, and cheaper treatment option for people with asthma or allergic rhinitis.
Introdução: O montelucaste, um antagonista seletivo e ativo dos receptores de leucotrienos, é um dos agentes mais comumente usados na prática clínica no tratamento da asma, tanto em adultos quanto em crianças. Objetivo: Avaliar se os perfis farmacocinéticos de duas formulações de montelucaste eram semelhantes após uma dose única de comprimidos mastigáveis de 5 mg, administrados por via oral em jejum, coletando amostras de sangue desde antes da administração até 36 horas depois disso. Métodos: Estudo comparativo randomizado, 2 sequências e 2 períodos, cruzado, de dois medicamentos em comprimidos mastigáveis: Singulair®, fornecido pela Merck Sharp e Dohme Farmacêutica Ltda. (referência) e Montelucaste 5 mg, fabricado pela Eurofarma Laboratórios S.A. (teste). Amostras de plasma obtidas de 35 indivíduos elegíveis foram analisadas para montelucaste por cromatografia líquida de alta eficiência acoplada a espectrometria de massa em tandem, tendo Montelucaste-d6 como padrão interno. As concentrações máximas de montelucaste foram 299,313±11,039 ng/mL para referência e 279,803±10,085 ng/mL para formulação de teste. Resultados: A análise estatística não mostrou diferenças significativas para AUC0-36h, AUC0-inf e nem para Cmax entre as formulações, apresentando as razões Teste/Referência: 102,458 para AUC0-36h, 102,522 para AUC0-inf e 93,490 para Cmax. Nenhum evento adverso grave foi relatado durante o estudo. De acordo com a regulamentação brasileira, o atual estudo farmacocinético demonstrou bioequivalência entre os agentes individuais e forneceu evidências de bioequivalência entre Singulair® e Montelukast fabricado pela Eurofarma. Resultado: Os resultados mostraram que os novos comprimidos genéricos são clinicamente seguros e podem ser trocados pela marca original. O montelucaste da Eurofarma oferece uma opção de tratamento mais barata, segura e eficaz para indivíduos com asma ou rinite alérgica.
Subject(s)
Humans , Adolescent , Adult , Middle AgedABSTRACT
Capecitabine is a prodrug and is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil, by thymidine phosphorylase, which is generally expressed at high levels in tumors. Clinical and pharmacokinetic studies of capecitabine have been performed in patients with cancer. This study aims to evaluate the bioequivalence of two capecitabine formulations (150-mg tablet) using healthy male subjects under nonfasting conditions. The study was conducted as an open, randomized, three-period, semi-replicated design with three sequences (RRT, RTR, TRR) with a 1-week washout interval. The subjects were selected for the study after having their health status previously assessed by a clinical evaluation and laboratory tests (biochemical and hematological parameters, and urinalysis). A single capecitabine tablet (150 mg) was given in each occasion. Plasma capecitabine concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM). The geometric mean and 90% confidence intervals (CI) of capecitabine/Xeloda® (T/R) percent ratio were 104.34% (98.74 - 110.25%) for AUClast, 103.06% (97.48 - 108.96%) for AUCinf, and 104.07% (88.13 - 122.90%) for Cmax. Since the 90% CI for Cmax, AUClast, and AUCinf ratios were all inside the 80 - 125% interval proposed by the US Food and Drug Administration Agency, it was concluded that the capecitabine formulation elaborated by Eurofarma Laboratórios Ltda. is bioequivalent to Xeloda® formulation for both the rate and the extent of absorption. The drug was well tolerated by the subjects, indicating that it is safe to perform capecitabine bioequivalence studies in healthy male subjects.â©.
