DEFAR - Artigos publicados em periódicos

URI permanente para esta coleçãohttp://www.hml.repositorio.ufop.br/handle/123456789/531

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2018 - 201912020 - 20211

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Autor: search.filters.author.González Álvarez, Isabel

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    Eremantholide C from aerial parts of Lychnophora trichocarpha, as drug candidate : fraction absorbed prediction in humans and BCS permeability class determination.
    (2021) Caldeira, Tamires Guedes; Guimarães, Dênia Antunes Saúde; González Álvarez, Isabel; Bermejo, Marival; Souza, Jacqueline de
    Background Lychnophora trichocarpha (Spreng.) Spreng. ex Sch.Bip has been used in folk medicine to treat pain, inflammation, rheumatism and bruises. Eremantholide C, a sesquiterpene lactone, is one of the substances responsible for the anti-inflammatory and anti-hyperuricemic effects of L. trichocarpha. Objectives Considering the potential to become a drug for the treatment of inflammation and gouty arthritis, this study evaluated the permeability of eremantholide C using in situ intestinal perfusion in rats. From the permeability data, it was possible to predict the fraction absorbed of eremantholide C in humans and elucidate its oral absorption process. Methods In situ intestinal perfusion studies were performed in the complete small intestine of rats using different concentrations of eremantholide C: 960 μg/ml, 96 μg/ml and 9.6 μg/ml (with and without sodium azide), in order to verify the lack of dependence on the measured permeability as a function of the substance concentration in the perfusion solutions. Results Eremantholide C showed Peff values, in rats, greater than 5 × 10−5 cm/s and fraction absorbed predicted for humans greater than 85%. These results indicated the high permeability for eremantholide C. Moreover, its permeation process occurs only by passive route, because there were no statistically significant differences between the Peff values for eremantholide C. Conclusion The high permeability, in addition to the low solubility, indicated that eremantholide C is a biologically active substance BCS class II. The pharmacological activities, low toxicity and biopharmaceutics parameters demonstrate that eremantholide C has the necessary requirements for the development of a drug product, to be administered orally, with action on inflammation, hyperuricemia and gout.
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    Determination of intestinal permeability using in situ perfusion model in rats : challenges and advantages to BCS classification applied to digoxin.
    (2018) Caldeira, Tamires Guedes; Ruiz Picazo, Alejandro; Lozoya Agullo, Isabel; Guimarães, Dênia Antunes Saúde; González Álvarez, Marta; Souza, Jacqueline de; González Álvarez, Isabel; Bermejo, Marival
    The purpose of this work was to describe the closed loop in situ perfusion method in rats and to compare the difficulties and advantages with other methods proposed by regulatory agencies for BCS classification and finally to illustrate its application to evaluate the permeability of digoxin at relevant clinical concentrations. Digoxin was evaluated at two concentration levels: 1.0 μg/ml (with and without sodium azide 65.0 μg/ml) and 6.0 μg/ ml. These concentrations correspond to the ratio of the highest dose strength (0.25 mg) and the highest single dose administered (1.5 mg) and the 250 ml of water. In situ closed loop perfusion studies in rats were performed in the whole small intestine and also in duodenum, jejunum and ileum segments to evaluate the relevance of Pgp secretion in the overall permeability. A kinetic modelling approach involving passive permeation and efflux transport mechanism allowed the estimation of the passive diffusional component and the Michaelis-menten parameters. The estimated Km value demonstrated that at clinical luminal concentrations the efflux process is not saturated and then it could be inhibited by other drugs, excipients or food components leading to the already reported clinical drug-drug and drug-food interations. The present data confirms from a mechanistic point of view these interactions.