Estudio farmacocinético de quercetina-3-O-rutinósido a partir de un extracto estandarizado de cálices de Physalis peruviana en dos modelos animales

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dc.contributor.advisorAragón Novoa, Diana Marcelaspa
dc.contributor.advisorOliveira Simões, Claudia Mariaspa
dc.contributor.authorDomínguez Moré, Gina Paolaspa
dc.contributor.researchgroupSistemas para Liberación Controlada de Moléculas Biológicamente Activasspa
dc.date.accessioned2021-01-26T15:23:39Zspa
dc.date.available2021-01-26T15:23:39Zspa
dc.date.issued2020-12-04spa
dc.description.abstractPhysalis peruviana es una planta de la familia Solanaceae con propiedades medicinales. Un extracto hidroalcohólico de cálices de P. peruviana presentó actividad antiinflamatoria e hipoglicemiante. El objetivo de esta investigación fue estudiar la farmacocinética del flavonoide mayoritario del extracto, quercetina-3-O-rutinósido (rutina), en ratas y conejos, como parte del desarrollo preclínico de un fitoterapéutico. Se estudió inicialmente la permeabilidad intestinal de rutina desde el extracto, utilizando el modelo de Caco-2. El estudio farmacocinético se realizó tras la administración en los animales de dosis del extracto entre 100 y 1000 mg/kg, por vía i.v. y oral y la toma de muestras de sangre entre las 0 y las 48 h. Las muestras provenientes de los estudios de permeabilidad y farmacocinéticos se cuantificaron para rutina y sus metabolitos, utilizando técnicas HPLC y UHPLC-UV validadas. Se obtuvo también el coeficiente de permeabilidad aparente (Papp) y los parámetros farmacocinéticos de rutina estándar con fines comparativos. El Papp de rutina en el extracto fue mayor que el del compuesto puro (1.53 ± 0.07 vs 0.9 ± 0.03 x 10-5 cm/s). En los animales, rutina administrada por vía oral, como compuesto puro o en el extracto, estuvo sujeta a metabolismo intestinal y los compuestos encontrados en el plasma fueron principalmente los conjugados glucurónido y sulfato de quercetina (Q3OG y Q3OS respectivamente). La biodisponibilidad relativa oral de Q3OG y Q3OS desde el extracto fue 11.2 (1120%) en ratas y de 12.0 (1200%) en conejos, frente al compuesto puro. Se concluyó que la matriz del extracto tiene influencia sobre la permeabilidad y biodisponibilidad de rutina y sus metabolitos.spa
dc.description.abstractPhysalis peruviana is a plant of the Solanaceae family with medicinal properties. A hydroalcoholic extract from calyces of P. peruviana showed anti-inflammatory and hypoglycemic activity. The aim of this research was to study the pharmacokinetics of the main flavonoid in the extract, quercetin-3-O-rutinoside (rutin), in rats and rabbits, as part of the preclinical development of a botanical drug. Intestinal permeability of rutin from the extract was initially studied using the Caco-2 model. The pharmacokinetic study was carried out by administrating in the animals i.v. and oral doses of the extract among 100 and 1000 mg/kg and taking blood samples from 0 to 48 h. Samples from permeability and pharmacokinetic studies were quantified for rutin and its main metabolites, using validated HPLC and UHPLC-UV methods. Pure rutin was also assayed for permeability and pharmacokinetic for comparison purposes. The intestinal permeability of rutin in the extract was greater than that of the pure compound (1.53 ± 0.07 vs 0.9 ± 0.03 x 10-5 cm/s). In animals orally administered with rutin (pure or extract), the flavonoid was subject to intestinal metabolism and the compounds found in plasma were glucuronide and sulfate conjugates of quercetin (Q3OG and Q3OS respectively). The relative bioavailability of Q3Og y Q3OS in the extract versus the pure compound was up to 11.2 (1120%) in rats and 12.0 (1200%) in rabbits. It was concluded that the extract matrix influences the permeability and bioavailability of rutin and its metabolites.spa
dc.description.additionalLínea de Investigación: farmacocinética y estudios de biodisponibilidad y bioequivalencia.spa
dc.description.degreelevelDoctoradospa
dc.format.extent181spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.citationDomínguez, G. (2020). Estudio farmacocinético de quercetina-3-O-rutinósido a partir de un extracto estandarizado de cálices de Physalis peruviana en dos modelos animales [Tesis de doctorado, Universidad Nacional de Colombia]. Repositorio Institucional.spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/78924
dc.language.isospaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Farmaciaspa
dc.publisher.programBogotá - Ciencias - Doctorado en Ciencias Farmacéuticasspa
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dc.rightsDerechos reservados - Universidad Nacional de Colombiaspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacionalspa
dc.rights.spaAcceso abiertospa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.ddc615 - Farmacología y terapéuticaspa
dc.subject.ddc610 - Medicina y saludspa
dc.subject.proposalBiodisponibilidadspa
dc.subject.proposalBioavailabilityeng
dc.subject.proposalPermeabilidadspa
dc.subject.proposalPermeabilityeng
dc.subject.proposalExtracto vegetalspa
dc.subject.proposalPlant extracteng
dc.subject.proposalPharmacokineticseng
dc.subject.proposalFarmacocinéticaspa
dc.subject.proposalQuercetina-3-O-rutinósidospa
dc.subject.proposalQuercetin-3-O-rutinosideeng
dc.titleEstudio farmacocinético de quercetina-3-O-rutinósido a partir de un extracto estandarizado de cálices de Physalis peruviana en dos modelos animalesspa
dc.typeTrabajo de grado - Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06spa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/doctoralThesisspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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Doctorado en Ciencias Farmacéuticas