{"id":114615,"date":"2013-06-09T00:00:00","date_gmt":"2013-06-09T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-farmacocinetico-de-formulaciones-polimericas-de-liberacion-controlada-para-enrofloxacino-en-ovino\/"},"modified":"2013-06-09T00:00:00","modified_gmt":"2013-06-09T00:00:00","slug":"estudio-farmacocinetico-de-formulaciones-polimericas-de-liberacion-controlada-para-enrofloxacino-en-ovino","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/farmacologia\/estudio-farmacocinetico-de-formulaciones-polimericas-de-liberacion-controlada-para-enrofloxacino-en-ovino\/","title":{"rendered":"Estudio farmacocinetico de formulaciones polim\u00e9ricas de liberacion controlada para enrofloxacino en ovino"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Mar\u00eda  Luisa Gabarda Cassinello <\/strong><\/h2>\n<p>Objetivo: estudiar el comportamiento cin\u00e9tico de enrofloxacino y su metabolito, ciprofloxacino, en ovejas, tras la administraci\u00f3n por las v\u00edas intravenosa y subcut\u00e1nea de una dosis de 5 mg\/kg, y tras la administraci\u00f3n en soluci\u00f3n del pol\u00edmero p407 al 25% y en soluci\u00f3n del pol\u00edmero p407 al 25% + carboximetilcelulosa al 2% por v\u00eda subcut\u00e1nea a la dosis de 15 mg\/kg. metodos: la determinaci\u00f3n de enrofloxacino y de ciprofloxacino en plasma y leche se realiz\u00f3 mediante hplc con detecci\u00f3n fluorescente, siguiendo el m\u00e9todo descrito por siefert y cols. (1999). El ajuste a m\u00e9todos farmacocin\u00e9ticos compartimentales y no compartimentales se realiz\u00f3 mediante el programa winnonlin professional\u00c2\u00bf y multifit\u00c2\u00bf (proost, 1997). El criterio utilizado para determinar cu\u00e1l era la ecuaci\u00f3n que mejor describ\u00eda la evoluci\u00f3n de los datos experimentales en cada caso, fue el criterio de informaci\u00f3n de akaike (aic) (yamaoka y cols., 1978).  resultados: tras la administraci\u00f3n intravenosa, enrofloxacino y ciprofloxacino se distribuyen seg\u00fan un modelo bicompartimental abierto, al igual que para las v\u00edas extravasculares. Tras la administraci\u00f3n intravenosa, la vida media obtenida para el enrofloxacino (t1\/2?Z) fue de 8,11 \u00c2\u00b1 2,22 h con un tiempo medio de residencia (mrt) de 5,41 \u00c2\u00b1 1,49 h. Los vol\u00famenes aparentes de distribuci\u00f3n de enrofloxacino calculados en funci\u00f3n del \u00e1rea bajo la curva (vz) y en estado estacionario (vss) resultaron ser de 0,89 \u00c2\u00b1 0,26 l\/kg y 2,01 \u00c2\u00b1 0,52 l\/kg respectivamente, indicando una amplia distribuci\u00f3n org\u00e1nica. Por lo que respecta al aclaramiento plasm\u00e1tico (cl), \u00e9ste alcanz\u00f3 un valor de  0,16 \u00c2\u00b1 0,03 l\/kg\u00c2\u00b7h. Cuando se administr\u00f3 el enrofloxacino v\u00eda subcut\u00e1nea sin pol\u00edmero, v\u00eda subcut\u00e1nea en soluci\u00f3n del pol\u00edmero p407 al 25% y v\u00eda subcut\u00e1nea en soluci\u00f3n del pol\u00edmero p407 al 25% + carboximetilcelulosa al 2%, se obtuvieron los siguientes tiempos de vida media: 13,00 \u00c2\u00b1 2,11, 34,80 \u00c2\u00b1 8,47 y 38,66 \u00c2\u00b1 8,97 h, respectivamente, con unos valores de mrt de 7,92 \u00c2\u00b1 0,67, 20,74 \u00c2\u00b1 3,57 y 22,71 \u00c2\u00b1 2,32 h, respectivamente. La biodisponibilidad de enrofloxacino cuando se administr\u00f3 por v\u00eda subcut\u00e1nea sin pol\u00edmero, alcanz\u00f3 un valor de 104,72 \u00c2\u00b1 24,45 %. Valores algo inferiores se obtuvieron cuando se administr\u00f3 el enrofloxacino v\u00eda subcut\u00e1nea en soluci\u00f3n del pol\u00edmero p407 al 25% y en soluci\u00f3n del pol\u00edmero p407 al 25% + carboximetilcelulosa al 2%,  que fueron de 82,01 \u00c2\u00b1 22,06 % y 84,01 \u00c2\u00b1 21,57 %, respectivamente. En cuanto al metabolito de ciprofloxacino, tras la adminstraci\u00f3n intravenosa de enrofloxacino la vida media de ciprofloxacino fue de 6,83 \u00c2\u00b1 3,00 h con un valor de mrt de 6,36 \u00c2\u00b1 1,71h. Cuando se administr\u00f3 el enrofloxacino v\u00eda subcut\u00e1nea sin pol\u00edmero, v\u00eda subcut\u00e1nea en soluci\u00f3n del pol\u00edmero p407 al 25% y v\u00eda subcut\u00e1nea en soluci\u00f3n del pol\u00edmero p407 al 25% + carboximetilcelulosa al 2%, se registraron los siguientes tiempos de vida media para su metabolito ciprofloxacino: 10,62\t \u00c2\u00b1 4,35, 7,15 \u00c2\u00b1 5,44 y 20,61 \u00c2\u00b1 6,06 h, respectivamente, con unos valores de mrt de 11,90 \u00c2\u00b1 2,05, 16,78 \u00c2\u00b1 3,77 y 21,39 \u00c2\u00b1 4,85h, respectivamente.Se determinaron las concentraciones m\u00ednimas inhibitorias de enrofloxacino y de ciprofloxacino frente a cepas de staphylococcus aureus, a fin de determinar los \u00edndices farmacocin\u00e9tico-farmacodin\u00e1micos \u00f3ptimos.  conclusiones: de dicho estudio se puede concluir que una dosis de 15 mg\/kg podr\u00eda ser efectiva por v\u00eda subcut\u00e1nea cuando se administre junto con pol\u00edmero p407 al 25% o junto con pol\u00edmero p407 al 25% + carboximetilcelulosa al 2%, en ovejas contra aislados bacterianos con cmi   0,5 \u00c2\u00b5g\/ml. La penetraci\u00f3n en leche de enrofloxacino alcanz\u00f3 unos ratios bajos, con unas relaciones aucleche\/aucplasma  cercanas a 0,5 en las v\u00edas subcut\u00e1neas y de 1 en la v\u00eda intravenosa. En el ciprofloxacino alcanz\u00f3 unos ratios elevados, alcanzando relaciones del 10-20.  objective. To study the pharmacokinetics of enrofloxacin and its metabolite, ciprofloxacin, were studied following intravenous and subcutaneous administration of single doses of 5 mg\/kg to healthy sheeps, and as a long-acting poloxamer 407 gel formulation and poloxamer 407 + carboxymethylcellulose. methods: plasma concentrations were determined by hplc assay with fluorescence detection following the method described by siefert et al. (1999). The fitting to compartmental and non compartimental pharmacokinetic methods was carried out by using winnonlin professional\u00c2\u00bf computers programmes. The akaike&apos;s information criterion (aic) (yamaoka et al., 1978) was used to select the best equation that defines plasma concentration-time data for each animal.  results: the enrofloxacin plasma concentration versus time data after intravenous and extravascular administrations could best be described by a two compartment open model.The enrofloxacin terminal half-life (t\u00c2\u00bf z) was 8,11hh after intravenous administration, with a mean residence time (mrt) of 5,41 h. The apparent volumes of distribution calculated by the area method (vz) and at steady-state (vss) were 0,89 and 2,01  l\/kg, respectively, indicating a wide body distribution. Total body clearance was 0,16 l\/kg\u00c2\u00b7h. The ciprofloxacin terminal half-life (t\u00c2\u00bf z) was 6,83 h after intravenous administration, with a mean residence time (mrt)  of 6,36 h. After extravascular administrations, terminal half-lives were 13,00, 34,80 and 38,66 h for enrofloxacin administration subcutaneously without poloxamer, with long-acting poloxamer 407 gel formulation and  with poloxamer 407 + carboxymethylcellulose, respectively. Mrt values obtained were 4,08, 7,58 and 7,16 h respectively. Terminal half-lives were 10,62, 7,15 and 20,61 h for ciprofloxacin metabolite,   after enrofloxacin extravascular administrations, subcutaneously without poloxamer, with long-acting poloxamer 407 gel formulation and  with poloxamer 407 + carboxymethylcellulose  respectively. Mrt values obtained were 11,90, 16,78 and 21,39 h respectively. Absolute bioavailability was104,72 % after enrofloxacin subcutaneous administration. Similar values were obtained, 82, 01 % and y 84,01 %, after enrofloxacin administration subcutaneously with long-acting poloxamer 407 gel formulation and  with poloxamer 407 + carboxymethylcellulose, respectively. Minimal inhibitory concentrations (mic) assays of enrofloxacin against different strains of staphylococcus aureus were performed in order to compute pharmacodynamic surrogate markers.  conclusion: it can be concluded from this study that a dosing r\u00e9gimen of 15 mg\/kg could be effective by subcutaneous route with polymer p407 (25%) with or without carboximetylcelulose (2%) in sheep against staphylococcus aureus isolates with mics   0,5 \u00c2\u00b5g\/ml.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio farmacocinetico de formulaciones polim\u00e9ricas de liberacion controlada para enrofloxacino en ovino<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio farmacocinetico de formulaciones polim\u00e9ricas de liberacion controlada para enrofloxacino en ovino <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Mar\u00eda  Luisa Gabarda Cassinello <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 06\/09\/2013<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Emilio Fern\u00e1ndez Var\u00f3n<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Juan  manuel Serrano caballero <\/li>\n<li>Mar\u00eda  rosa Caro vergara (vocal)<\/li>\n<li>ruperto Bermejo rom\u00e1n (vocal)<\/li>\n<li>Juan  Manuel Serrano rodr\u00edguez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Mar\u00eda Luisa Gabarda Cassinello Objetivo: estudiar el comportamiento cin\u00e9tico de enrofloxacino y su metabolito, ciprofloxacino, en ovejas, [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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