{"id":117771,"date":"2015-02-07T00:00:00","date_gmt":"2015-02-07T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-de-estabilidad-y-evaluacion-de-la-toxicidad-de-mezclas-estandarizadas-de-terapia-triple-intratecal-con-metotrexato-citarabina-e-hidrocortisona\/"},"modified":"2015-02-07T00:00:00","modified_gmt":"2015-02-07T00:00:00","slug":"estudio-de-estabilidad-y-evaluacion-de-la-toxicidad-de-mezclas-estandarizadas-de-terapia-triple-intratecal-con-metotrexato-citarabina-e-hidrocortisona","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/analisis-de-farmacos\/estudio-de-estabilidad-y-evaluacion-de-la-toxicidad-de-mezclas-estandarizadas-de-terapia-triple-intratecal-con-metotrexato-citarabina-e-hidrocortisona\/","title":{"rendered":"Estudio de estabilidad y evaluaci\u00f3n de la toxicidad de mezclas estandarizadas de terapia triple intratecal con metotrexato, citarabina e hidrocortisona."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Raquel Olmos Jimenez <\/strong><\/h2>\n<p>Objetivos:  los objetivos principales del estudio fueron:  1) estudiar la estabilidad fisicoqu\u00edmica, en condiciones de uso, de cuatro mezclas estandarizadas triple intratecales (tit) de metotrexato, citarabina e hidrocortisona conservadas a temperatura ambiente y en refrigeraci\u00f3n.  2) evaluar la toxicidad de la administraci\u00f3n de tratamiento triple intratecal estandarizado como profilaxis y tratamiento de la enfermedad leptomen\u00edngea en pacientes adultos y pedi\u00e1tricos. metodolog\u00eda:  la estabilidad qu\u00edmica de la muestra se midi\u00f3 por triplicado mediante cromatograf\u00eda l\u00edquida de alta eficacia a las 0, 3, 6, 12 y 24 horas y 2, 4, 5, 6 y 7 d\u00edas de las mezclas conservadas a temperatura ambiente y bajo refrigeraci\u00f3n, se determin\u00f3 tambi\u00e9n a esos tiempo el ph y la osmolaridad de las mezclas. La concentraci\u00f3n de f\u00e1rmacos a tiempo 0 se defini\u00f3 como el 100% y se consider\u00f3 que los f\u00e1rmacos eran estables qu\u00edmicamente si la concentraci\u00f3n era igual o mayor al 90% de la inicial. Los valores de ph y osmolaridad aceptados como v\u00e1lidos fueron cercanos al rango fisiol\u00f3gico del l\u00edquido cefalorraqu\u00eddeo, consider\u00e1ndose las mezclas triple intratecales estables si el rango de ph y osmolaridad era de 7-7,5 y de 280-310 mosm\/kg, respectivamente. la evaluaci\u00f3n de la toxicidad se realiz\u00f3 de forma prospectiva en todos los pacientes adultos y pedi\u00e1tricos a los que se les administr\u00f3 quimioterapia tit estandarizada para el tratamiento o la profilaxis de la enfermedad leptomen\u00edngea en el hospital universitario virgen de la arrixaca desde el 1 de enero de 2013 hasta el 31 de julio de 2014 (18 meses). Se realiz\u00f3 un seguimiento de todos los pacientes desde la administraci\u00f3n de la primera tit del estudio hasta el 31 de julio de 2014, excepto exitus. Los eventos adversos fueron detectados por el m\u00e9dico responsable del paciente y registrados por el investigador principal. La definici\u00f3n y gradaci\u00f3n de los eventos adversos se realiz\u00f3 seg\u00fan la escala ctcae v.4.0. conclusiones:  1) las concentraciones de metotrexato s\u00f3dico, citarabina e hidrocortisona fosfato s\u00f3dico de las cuatro mezclas triple intratecales estandarizadas, conservadas a 25\u00c2\u00bac y 2-8\u00c2\u00bac no variaron m\u00e1s del 10% respecto a las concentraciones iniciales a ninguno de los tiempos de medida, consider\u00e1ndose estables qu\u00edmicamente durante, al menos, 7 d\u00edas. La osmolaridad de las mezclas se mantuvo durante los 7 d\u00edas de estudio, mientras que el ph se situ\u00f3 dentro de rango de estudio durante 5-7 d\u00edas en las mezclas refrigeradas y 48-96 horas en las conservadas a temperatura ambiente, en funci\u00f3n de la mezcla. 2) en los pacientes pedi\u00e1tricos, se ha observado toxicidad en el 56,1% de los pacientes y el 16,7% de las administraciones y en los pacientes adultos se ha observado toxicidad en el 70% de los pacientes y el 39,3% de las administraciones. La toxicidad mayoritaria en los pacientes pedi\u00e1tricos fue la emesis, seguida de cefalea y dolor lumbar y en los adultos la cefalea, seguido de la emesis y la aparici\u00f3n de v\u00e9rtigos. La mayor\u00eda de los eventos adversos detectados durante el periodo de estudio, en la poblaci\u00f3n global, fueron de grado 1-2. La frecuencia de aparici\u00f3n de toxicidad grado 3 fue del 4,9% en pacientes pedi\u00e1tricos y 3,2% en adultos. No se detectaron reacciones adversas de grado 4-5.   objectives: the main objectives of the study were: 1) study the physicochemical stability of four standard triple intrathecal (tit) mixtures of methotrexate, cytarabine and hydrocortisone stored at room temperature and refrigerated. 2) evaluate the toxicity of intrathecal administration of standard triple therapy for prophylaxis and treatment of leptomeningeal disease in adults and pediatric patients. methodology: the chemical stability of the sample was measured in triplicate by high-performance liquid chromatography at 0, 3, 6, 12 and 24 hours and 2, 4, 5, 6 and 7 days preserving the samples at room temperature and under refrigeration, ph and osmolarity of the mixtures were also determined at such time. The drug concentration at time 0 was defined as 100% and the drugs were considered chemically stable if the concentration was equal or greater than 90% of the initial. The ph and osmolarity were accepted as valid close to the physiological range of cerebrospinal fluid, considered stable triple mixtures intrathecal if the range of ph and osmolality was 7-7,5 and 280-310 mosm\/ kg, respectively. the toxicity evaluation was performed prospectively in all adult and pediatric patients who were administered chemotherapy tit standardized for the treatment or prophylaxis of leptomeningeal disease at the university arrixaca hospital from 1st of january 2013 to 31st of july 2014 (18 months). The monitoring of all patients was performed from the administration of the first tit study until 31st of july 2014, except for death. Adverse events were detected by the attending physician and recorded by the principal investigator. The definition and grading of adverse events was performed according to ctcae v.4.0 scale. conclusions: 1) the concentrations of sodium methotrexate, cytarabine and hydrocortisone sodium phosphate of the four triple intrathecal standardized mixtures, preserved at 25 \u00c2\u00b0 c and 2-8\u00c2\u00bac did not vary more than 10% compared to the initial concentrations any of the measured times, considering chemically stable for at least 7 days. Osmolarity mixtures remained during the 7 day of the study, while the ph was within range study for 5-7 days in refrigerated mixtures and 48-96 hours in room temperature ones, depending on the mixture. 2) in pediatric patients, toxicity has been observed in 56,1% of patients and 16,7% of administrations while in adult patients toxicity has been observed in 70% of patients and 39,3 % of administrations. The major toxicity in pediatric patients was emesis, followed by headache and low back pain and in adults was headache, followed by the appearance of emesis and dizziness. Most adverse events detected during the study period, in the overall population, were grade 1-2. The frequency of grade 3 toxicity was 4.9% in pediatric patients and 3.2% in adults. No grade 4-5 adverse reactions were detected.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio de estabilidad y evaluaci\u00f3n de la toxicidad de mezclas estandarizadas de terapia triple intratecal con metotrexato, citarabina e hidrocortisona.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio de estabilidad y evaluaci\u00f3n de la toxicidad de mezclas estandarizadas de terapia triple intratecal con metotrexato, citarabina e hidrocortisona. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Raquel Olmos Jimenez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 02\/07\/2015<\/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>M. Sacramento Diaz Carrasco<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Francisco Gil cano <\/li>\n<li>Miguel angel Calleja hernandez (vocal)<\/li>\n<li>Jos\u00e9 Antonio Noguera velasco (vocal)<\/li>\n<li>asunci\u00f3n Albert mar\u00ed (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Raquel Olmos Jimenez Objetivos: los objetivos principales del estudio fueron: 1) estudiar la estabilidad fisicoqu\u00edmica, en condiciones [&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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[339,36572,2445,8235],"tags":[57427,46004,224729,102885,44016,231894],"class_list":["post-117771","post","type-post","status-publish","format-standard","hentry","category-analisis-de-farmacos","category-estandarizacion-de-farmacos","category-evaluacion-de-farmacos","category-murcia","tag-asuncion-albert-mari","tag-francisco-gil-cano","tag-jose-antonio-noguera-velasco","tag-m-sacramento-diaz-carrasco","tag-miguel-angel-calleja-hernandez","tag-raquel-olmos-jimenez"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/117771","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=117771"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/117771\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=117771"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=117771"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=117771"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}