{"id":114035,"date":"2013-09-04T00:00:00","date_gmt":"2013-09-04T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/pharmacokinetic-pharmacodynamic-modelling-during-development-of-novel-drugs-for-the-treatment-of-sleep-disorders\/"},"modified":"2013-09-04T00:00:00","modified_gmt":"2013-09-04T00:00:00","slug":"pharmacokinetic-pharmacodynamic-modelling-during-development-of-novel-drugs-for-the-treatment-of-sleep-disorders","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/matematicas\/pharmacokinetic-pharmacodynamic-modelling-during-development-of-novel-drugs-for-the-treatment-of-sleep-disorders\/","title":{"rendered":"Pharmacokinetic\/pharmacodynamic modelling during development of novel drugs for the treatment of sleep disorders"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Arianna Madrid Aispuro <\/strong><\/h2>\n<p>Pharmacokinetic\/pharmacodynamic modelling during development of novel drugs for the treatment of sleep disorders  arianna Madrid aispuro school of pharmacy; department of pharmacy and pharmaceutical technology university of navarra (spain) 2013  the goal of the present work was to describe the sleep effects of the hypnotic drug zolpidem in rats using a semi-mechanistic pharmacokinetic-pharmacodynamic (pk\/pd) markov-chain model.  data were obtained from healthy sprague-dawley rats in which eeg was continuously recorded for at least two days of alternating dark\/light cycles. For each 10 second interval, eeg data were converted into awake, rem or nrem stages. After a baseline period, methylcellulose (mc), zolpidem at doses of 10, 20 or 30 mg\/kg was administered orally.  the time course of the nine possible transition probabilities was  described using a non-homogeneous markov chain model based on piecewise multinomial logistic functions. Model building was performed in three steps: (i) baseline data was described first, then (ii) the model accounting for the mc effects was built, finally (iii) the pk\/pd model describing zolpidem effects was developed.  exploration of the time course of raw transition probabilities revealed that zolpidem elicited an initial time dependent decrease in the transition probability from nrem to awake, and an increase at later times which is interpreted as a rebound effect. Drug effects including the rebound phenomena were described with a turnover feedback model.  the current analysis shows an application of the multinomial logistic approach applied to markov chain models. The model presented here represents an integrated model including baseline, saline, and drug effect models. This type of approach supports the identification and the quantitative description of feedback mechanisms, and represents a promise approach to extract pharmacodynamic characteristics of different classes of sleep drugs.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Pharmacokinetic\/pharmacodynamic modelling during development of novel drugs for the treatment of sleep disorders<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Pharmacokinetic\/pharmacodynamic modelling during development of novel drugs for the treatment of sleep disorders <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Arianna Madrid Aispuro <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 09\/04\/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>Jos\u00e9 Ignacio Fernandez De Troconiz<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Marta Valle cano <\/li>\n<li>Mar\u00eda isabel Gonz\u00e1lez alvarez (vocal)<\/li>\n<li>Jos\u00e9 martin Pastor gutierrez (vocal)<\/li>\n<li>arantxazu Isla ruiz (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Arianna Madrid Aispuro Pharmacokinetic\/pharmacodynamic modelling during development of novel drugs for the treatment of sleep disorders arianna [&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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