Estudo de perda do princípio ativo capecitabina e atividade citotóxica de preparo destinado à administração em forma líquida

• Ano de defesa: 2023
• Autor(a) principal: Coelho Júnior, Eliezer do Carmo
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Bioquímica; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Bioquímica
• Palavras-chave em Português: Câncer de mama; Capecitabina; Off-label; Timidina fosforilase; Farmacologia Bioquímica e Molecular
• Link de acesso: http://repositorio.ufes.br/handle/10/12569

Currently considered a serious global public health problem, cancer is defined as a group of diseases characterized by uncontrolled growth and spread of abnormal cells anywhere in the body. Metastatic breast cancer is the most severe form of this type of cancer and is considered incurable with currently available treatments aimed at preserving the quality of life of patients and providing the longest possible period without disease symptoms. One treatment option is capecitabine, a prodrug of the antineoplastic agent 5-Fluorouracil (5-FU), which is absorbed in the intestine after being administered in tablet form. After absorption, capecitabine is metabolized into its active form, 5-FU, by liver enzymes, causing cytotoxic effects on cancer cells. Despite the advantages of capecitabine being an orally administered drug, some patients may encounter difficulty in swallowing the capecitabine tablet, leading to off-label administration, for which there are currently no studies. Thus, this research aims to investigate whether there is a loss of the active ingredient capecitabine and, consequently, a decrease in its cytotoxic effect in an off-label administration. The results showed no decrease in the concentration of the active ingredient capecitabine in the solution prepared from the tablets in an analytical assay by UFLC within 360 minutes. Furthermore, a significant cytotoxic effect was observed in the MTT assay after treating breast cancer cell lines MCF-7 and MDA-MB-231 with the prepared solution, suggesting that the cytotoxic effect is maintained when using the solution for treatment for at least 120 minutes after preparation. The activity of the thymidine phosphorylase was determined in the MCF-7 and MDA-MB-231 cell lines, confirming the presence of this enzyme in these lines. It was observed that, in comparison to the MCF-7 line, the MDA-MB-231 line has higher activity of this enzyme (26.6%). It is suggested that the metabolic pathway for the conversion of capecitabine to 5-FU may not be exclusively dependent on the action of hepatic carboxylesterases.