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#mega-menu-max_mega_menu_1>li.mega-menu-item>a.mega-menu-link:hover{background:rgba(0,0,0,0);color:#081f2d;font-weight:400;text-decoration:none;border-color:transparent}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-row>ul.mega-sub-menu>li.mega-menu-columns-3-of-12{width:25%}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-columns-3-of-12{width:25%}}@media only screen and (max-width:1230px){#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-item.mega-toggle-on>a.mega-menu-link{color:#fff;background:#222}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-item{display:list-item;margin:0;clear:both;border:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-item>a.mega-menu-link{border-radius:0;border:0;margin:0;line-height:40px;height:40px;padding:0 10px;background:0 0;text-align:left;color:#fff;font-size:18px}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-row>ul.mega-sub-menu>li.mega-menu-column{width:100%;clear:both}}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-row .mega-menu-column>ul.mega-sub-menu>li.mega-menu-item{padding:0 15px 15px;width:100%}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu{z-index:999;border-radius:0;background:rgba(0,0,0,0);border:0;padding:0;position:absolute;width:100%;max-width:none;left:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item ul.mega-sub-menu{clear:both}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item ul.mega-sub-menu li.mega-menu-item ul.mega-sub-menu{margin-left:10px}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu ul.mega-sub-menu ul.mega-sub-menu{margin-left:10px}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item{color:#666;font-family:inherit;font-size:18px;display:block;float:left;clear:none;padding:0 15px 15px;vertical-align:top}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item.mega-menu-clear,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item.mega-menu-clear{clear:left}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link{color:#00a5c8;font-family:inherit;font-size:18px;text-transform:none;text-decoration:none;font-weight:400;text-align:left;margin:0;padding:0;vertical-align:top;display:block;border-top:0 solid #00a5c8;border-left:0 solid #00a5c8;border-right:0px solid #00a5c8;border-bottom:2px solid #00a5c8}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link:hover,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link:hover{border-color:#00a5c8}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link:focus,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link:hover,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link:focus,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item>a.mega-menu-link:hover{color:#00a5c8;font-weight:400;text-decoration:none;background:rgba(0,0,0,0)}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link{color:#fff;font-family:inherit;font-size:18px;text-transform:none;text-decoration:none;font-weight:400;text-align:left;margin:0;padding:0;vertical-align:top;display:block;border:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link:hover,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link:hover{border-color:transparent}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link:focus,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu li.mega-menu-column>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link:hover,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link:focus,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item li.mega-menu-item>a.mega-menu-link:hover{color:#fff;font-weight:400;text-decoration:none;background:rgba(0,0,0,0)}@media only screen and (max-width:1230px){#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu{float:left;position:static;width:100%}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu{border:0;padding:10px;border-radius:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-megamenu>ul.mega-sub-menu>li.mega-menu-item{width:100%;clear:both}}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu{z-index:999;position:absolute;width:300px;max-width:none;padding:20px;border:0;background:rgba(0,0,0,0);border-radius:0}@media only screen and (max-width:1230px){#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu{float:left;position:static;width:100%;padding:0;border:0;border-radius:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item{clear:both}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item:first-child>a.mega-menu-link{border-top-left-radius:0;border-top-right-radius:0}}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item a.mega-menu-link{display:block;background:rgba(0,0,0,0);color:#fff;font-family:inherit;font-size:18px;font-weight:400;padding:0;line-height:35px;text-decoration:none;text-transform:none;vertical-align:baseline}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item:first-child>a.mega-menu-link{border-top-left-radius:0;border-top-right-radius:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item:last-child>a.mega-menu-link{border-bottom-right-radius:0;border-bottom-left-radius:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item a.mega-menu-link:focus,#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item a.mega-menu-link:hover{background:rgba(0,0,0,0);font-weight:400;text-decoration:none;color:#fff}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item ul.mega-sub-menu{position:absolute;left:100%;top:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-item-has-children>a.mega-menu-link>span.mega-indicator{display:inline-block;width:auto;background:0 0;position:relative;pointer-events:auto;left:auto;min-width:auto;font-size:inherit;padding:0;margin:0 0 0 6px;height:auto;line-height:inherit;color:inherit}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-item-has-children>a.mega-menu-link>span.mega-indicator:after{content:"";font-family:dashicons;font-weight:400;display:inline-block;margin:0;vertical-align:top;-webkit-font-smoothing:antialiased;-moz-osx-font-smoothing:grayscale;transform:rotate(0);color:inherit;position:relative;background:0 0;height:auto;width:auto;right:auto;line-height:inherit}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-item-has-children li.mega-menu-item-has-children>a.mega-menu-link>span.mega-indicator{float:right}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-item-has-children.mega-collapse-children.mega-toggle-on>a.mega-menu-link>span.mega-indicator:after{content:""}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-megamenu:not(.mega-menu-tabbed) li.mega-menu-item-has-children:not(.mega-collapse-children)>a.mega-menu-link>span.mega-indicator{display:none}@media only screen and (min-width:1231px){#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-flyout li.mega-menu-item a.mega-menu-link>span.mega-indicator:after{content:""}}@media only screen and (max-width:1230px){#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item:last-child>a.mega-menu-link{border-bottom-right-radius:0;border-bottom-left-radius:0}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item ul.mega-sub-menu{position:static;left:0;width:100%}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item ul.mega-sub-menu a.mega-menu-link{padding-left:20px}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1>li.mega-menu-flyout ul.mega-sub-menu li.mega-menu-item ul.mega-sub-menu ul.mega-sub-menu a.mega-menu-link{padding-left:30px}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-item-has-children>a.mega-menu-link>span.mega-indicator{float:right}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-item-has-children.mega-toggle-on>a.mega-menu-link>span.mega-indicator:after{content:""}#mega-menu-wrap-max_mega_menu_1 #mega-menu-max_mega_menu_1 li.mega-menu-item-has-children.mega-hide-sub-menu-on-mobile>a.mega-menu-link>span.mega-indicator{display:none}#mega-menu-wrap-max_mega_menu_1:after{content:"";display:table;clear:both}}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle{display:none;z-index:1;cursor:pointer;background:rgba(255,255,255,.1);border-radius:2px 2px 2px 2px;line-height:80px;height:80px;text-align:left;user-select:none;-webkit-tap-highlight-color:transparent;outline:0;white-space:nowrap}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle img{max-width:100%;padding:0}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-center,#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-left,#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-right{display:-webkit-box;display:-ms-flexbox;display:-webkit-flex;display:flex;-ms-flex-preferred-size:33.33%;-webkit-flex-basis:33.33%;flex-basis:33.33%}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-left{-webkit-box-flex:1;-ms-flex:1;-webkit-flex:1;flex:1;-webkit-box-pack:start;-ms-flex-pack:start;-webkit-justify-content:flex-start;justify-content:flex-start}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-left .mega-toggle-block{margin-left:6px}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-left .mega-toggle-block:only-child{margin-right:6px}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-center{-webkit-box-pack:center;-ms-flex-pack:center;-webkit-justify-content:center;justify-content:center}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-center .mega-toggle-block{margin-left:3px;margin-right:3px}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-right{-webkit-box-flex:1;-ms-flex:1;-webkit-flex:1;flex:1;-webkit-box-pack:end;-ms-flex-pack:end;-webkit-justify-content:flex-end;justify-content:flex-end}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-right .mega-toggle-block{margin-right:6px}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-blocks-right .mega-toggle-block:only-child{margin-left:6px}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-block{display:-webkit-box;display:-ms-flexbox;display:-webkit-flex;display:flex;height:100%;outline:0;-webkit-align-self:center;-ms-flex-item-align:center;align-self:center;-ms-flex-negative:0;-webkit-flex-shrink:0;flex-shrink:0}@media only screen and (max-width:1230px){#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle{display:-webkit-box;display:-ms-flexbox;display:-webkit-flex;display:flex}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle+#mega-menu-max_mega_menu_1{background:#222;padding:1rem;display:none;position:absolute;width:100%;z-index:9999999}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle.mega-menu-open+#mega-menu-max_mega_menu_1{display:block}}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-block-0{cursor:pointer}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-block-0 .mega-toggle-animated{padding:0;display:-webkit-box;display:-ms-flexbox;display:-webkit-flex;display:flex;cursor:pointer;transition-property:opacity,filter;transition-duration:.15s;transition-timing-function:linear;font:inherit;color:inherit;text-transform:none;background-color:transparent;border:0;margin:0;overflow:visible;transform:scale(.8);align-self:center;outline:0;background:0 0}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-block-0 .mega-toggle-animated-box{width:40px;height:24px;display:inline-block;position:relative;outline:0}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-block-0 .mega-toggle-animated-inner{display:block;top:50%;margin-top:-2px}#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-block-0 .mega-toggle-animated-inner,#mega-menu-wrap-max_mega_menu_1 .mega-menu-toggle .mega-toggle-block-0 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<input class="search__qry" id="searchright" type="search" name="s" placeholder="Search"> <label class="search__button" for="searchright"> <svg xmlns:xlink="http://www.w3.org/1999/xlink"> <title>Search icon</title> <use xlink:href="#icon-search"></use> </svg> </label> </form> </div>       </div> </div> </header> <div class="hero"> <div class="hero__top" style="background-image: url('https://symeres.com/wp-content/uploads/2023/06/Hero-Image-Adme-1.jpg');"> <div class="hero__content"> <div class="hero__heading"> <svg xmlns:xlink="http://www.w3.org/1999/xlink"><use xlink:href="#icon-services-admetox"></use></svg> <h1>Admescope ADME-Tox</h1> </div> </div> </div> </div> <main class="wp-block-group main main--page is-layout-flow wp-block-group-is-layout-flow"> <div class="wp-block-group main__content is-layout-constrained wp-block-group-is-layout-constrained"> <div id="ez-toc-container" class="ez-toc-v2_0_69_1 counter-flat ez-toc-counter ez-toc-grey ez-toc-container-direction"> <div class="ez-toc-title-container"> <p class="ez-toc-title" style="cursor:inherit">Table of Contents</p> <span class="ez-toc-title-toggle"></span></div> <nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-1" href="#Introduction" title="Introduction">Introduction</a></li><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-2" href="#Physicochemistry_and_binding" title="Physicochemistry and binding">Physicochemistry and binding</a></li><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-3" href="#Permeability_and_transporters" title="Permeability and transporters">Permeability and transporters</a></li><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-4" href="#In_vitro_metabolism" title="In vitro metabolism">In vitro metabolism</a></li><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-5" href="#Drug_Interactions" title="Drug Interactions">Drug Interactions</a></li><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-6" href="#In_vitro_toxicology" title="In vitro toxicology">In vitro toxicology</a></li><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-7" href="#In_vivo_drug_metabolism_and_pharmacokinetics" title="In vivo drug metabolism and pharmacokinetics">In vivo drug metabolism and pharmacokinetics</a></li><li class='ez-toc-page-1'><a class="ez-toc-link ez-toc-heading-8" href="#Safety_metabolism_and_in_vivo_MetID" title="Safety metabolism and in vivo MetID">Safety metabolism and in vivo MetID</a></li></ul></nav></div> <div class="entry-content wp-block-post-content is-layout-flow wp-block-post-content-is-layout-flow"> <h2 class="wp-block-heading"><span class="ez-toc-section" id="Introduction"></span><strong>Introduction</strong><span class="ez-toc-section-end"></span></h2> <p class="has-medium-font-size"><strong>We can support your pharmaceutical discovery and development programs even further with our Admescope platform of high quality <em>in vitro</em> ADME-Tox profiling platform and<em> in vivo</em> DMPK services.</strong></p> <p class="has-medium-font-size">Our Symeres Admescope platform has an early ADME panel co-located with our medicinal chemistry laboratories in the Netherlands to support our integrated optimization projects.</p> <p class="has-medium-font-size">We have a far larger suite of customizable <em>in vitro</em> ADME-Tox and <em>in vivo</em> DMPK services at our Admescope laboratories in Finland that supports both discovery and development-stage small molecule and biologics projects.</p> <p class="has-medium-font-size">It is crucial to conduct the right studies at the right time to manage costs, for fast decision-making and to reduce the risk for failure at later stages of a project.</p> <h2 class="wp-block-heading"><span class="ez-toc-section" id="Physicochemistry_and_binding"></span>Physicochemistry and binding<span class="ez-toc-section-end"></span></h2> <p class="has-medium-font-size">Physicochemical parameters give information about the “drug-likeness” of the compound, with respect to absorption from the intestine. Information about these properties is also valuable when planning optimum conditions for other <em>in vitro</em> ADME assays.</p> <ul class="wp-block-list"> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/physicochemistry-and-binding/#Lipophilicity_logPD">Lipophilicity</a> (shake flask method and RP-HPLC screening method)</li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/physicochemistry-and-binding/#Solubility">Solubility</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/physicochemistry-and-binding/#Stability_in_Plasma_Buffer_or_Biorelevant_Media">Stability in plasma, buffer or biorelevant media</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/physicochemistry-and-binding/#Plasma_Protein_Binding">Plasma protein binding</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/physicochemistry-and-binding/#Red_Blood_Cell_Binding">Red blood cell binding</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/physicochemistry-and-binding/#Tissue_Binding">Tissue binding</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/physicochemistry-and-binding/#Microsome_Hepatocyte_Binding">Microsome/Hepatocyte binding</a></li> </ul> <div style="height:10px" aria-hidden="true" class="wp-block-spacer"></div> <div style="height:30px" aria-hidden="true" class="wp-block-spacer"></div> <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" /> <h2 class="wp-block-heading"><span class="ez-toc-section" id="Permeability_and_transporters"></span>Permeability and transporters<span class="ez-toc-section-end"></span></h2> <p class="has-medium-font-size">Several assays are available for evaluating permeability and identifying drug transporter substrates or inhibitors.</p> <ul class="wp-block-list"> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/permeability-and-transporters/#Parallel_Artificial_Membrane_Permeability_Assay_PAMPA">PAMPA (parallel artificial membrane permeability assay)</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/permeability-and-transporters/#Caco-2_MDCK_Permeability">Caco-2/MDCK permeability</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/permeability-and-transporters/#Efflux_Transporters">Efflux transporters</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/permeability-and-transporters/#Uptake_Transporters">Uptake transporters</a></li> </ul> <div style="height:10px" aria-hidden="true" class="wp-block-spacer"></div> <div style="height:30px" aria-hidden="true" class="wp-block-spacer"></div> <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" /> <h2 class="wp-block-heading"><span class="ez-toc-section" id="In_vitro_metabolism"></span><em>In vitro</em> metabolism<span class="ez-toc-section-end"></span></h2> <figure class="wp-block-image alignright size-full"><img decoding="async" width="337" height="386" src="data:image/svg+xml,%3Csvg%20xmlns='http://www.w3.org/2000/svg'%20viewBox='0%200%20337%20386'%3E%3C/svg%3E" alt="" class="wp-image-3411" data-lazy-srcset="https://symeres.com/wp-content/uploads/2023/06/in-vitro-metabolism-4.png 337w, https://symeres.com/wp-content/uploads/2023/06/in-vitro-metabolism-4-262x300.png 262w" data-lazy-sizes="(max-width: 337px) 100vw, 337px" data-lazy-src="https://symeres.com/wp-content/uploads/2023/06/in-vitro-metabolism-4.png" /><noscript><img decoding="async" width="337" height="386" src="https://symeres.com/wp-content/uploads/2023/06/in-vitro-metabolism-4.png" alt="" class="wp-image-3411" srcset="https://symeres.com/wp-content/uploads/2023/06/in-vitro-metabolism-4.png 337w, https://symeres.com/wp-content/uploads/2023/06/in-vitro-metabolism-4-262x300.png 262w" sizes="(max-width: 337px) 100vw, 337px" /></noscript></figure> <p class="has-medium-font-size">High-quality <em>in vitro</em> metabolism services are available to evaluate the metabolic fate of the compound in liver or extrahepatic tissues. The samples are analysed with state-of-the-art UPLC/HR-MS equipment.</p> <ul class="wp-block-list"> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Metabolic_Stability">Metabolic stability</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Metabolite_Identification_and_Profiling">Metabolite identification and profiling</a></li> <li class="has-medium-font-size"><a href="https://symeres.com/services/synthetic-chemistry/">Metabolite synthesis</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Phenotyping_of_Metabolizing_Enzymes">Identification of metabolising enzymes</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Non-CYP_Mediated_Metabolism">Non-CYP mediated metabolism</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Extrahepatic_Metabolism">Extrahepatic metabolism</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Metabolite_Production">Metabolite production and NMR identification</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Reactive_Metabolite_Screening">Reactive metabolite screening</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Acyl-Glucuronide_Reactivity">Acyl-Glucuronide reactivity</a></li> </ul> <div style="height:10px" aria-hidden="true" class="wp-block-spacer"></div> <div style="height:30px" aria-hidden="true" class="wp-block-spacer"></div> <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" /> <h2 class="wp-block-heading"><span class="ez-toc-section" id="Drug_Interactions"></span>Drug Interactions<span class="ez-toc-section-end"></span></h2> <p class="has-medium-font-size">Evaluating drug-drug interaction risk is a crucial part of drug safety evaluation required by the drug regulatory authorities. The available services cover the <a href="https://www.admescope.com/in-vitro-metabolism/identification-of-metabolising-enzymes.html">identification of metabolising enzymes</a>, enzyme inhibition and enzyme induction assays, as well as transporter-mediated drug-drug interactions.</p> <ul class="wp-block-list"> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/drug-interactions/#CYP_Inhibition">CYP inhibition</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/drug-interactions/#UGT_Inhibition">UGT inhibition</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/drug-interactions/#Inhibition_towards_other_Metabolising_Enzymes">Inhibition towards other metabolising enzymes</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/drug-interactions/#CYP_Induction">CYP induction</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/drug-interactions/#UGT_Induction">UGT induction</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/drug-interactions/#Transporter_Interactions">Transporter interactions</a></li> </ul> <figure class="wp-block-image size-full is-resized"><img decoding="async" src="data:image/svg+xml,%3Csvg%20xmlns='http://www.w3.org/2000/svg'%20viewBox='0%200%20340%20391'%3E%3C/svg%3E" alt="" class="wp-image-3391" width="340" height="391" data-lazy-srcset="https://symeres.com/wp-content/uploads/2023/06/Drug-interactions-Adme.jpg 336w, https://symeres.com/wp-content/uploads/2023/06/Drug-interactions-Adme-261x300.jpg 261w" data-lazy-sizes="(max-width: 340px) 100vw, 340px" data-lazy-src="https://symeres.com/wp-content/uploads/2023/06/Drug-interactions-Adme.jpg" /><noscript><img decoding="async" src="https://symeres.com/wp-content/uploads/2023/06/Drug-interactions-Adme.jpg" alt="" class="wp-image-3391" width="340" height="391" srcset="https://symeres.com/wp-content/uploads/2023/06/Drug-interactions-Adme.jpg 336w, https://symeres.com/wp-content/uploads/2023/06/Drug-interactions-Adme-261x300.jpg 261w" sizes="(max-width: 340px) 100vw, 340px" /></noscript></figure> <p class="has-medium-font-size"></p> <div style="height:10px" aria-hidden="true" class="wp-block-spacer"></div> <div style="height:30px" aria-hidden="true" class="wp-block-spacer"></div> <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" /> <h2 class="wp-block-heading"><span class="ez-toc-section" id="In_vitro_toxicology"></span><em>In vitro</em> toxicology<span class="ez-toc-section-end"></span></h2> <p class="has-medium-font-size">Information about <em>in vitro</em> toxicity early on during the drug discovery process support your internal decision making. The available non-GLP <em>in vitro</em> toxicology assays are planned for cost-efficient screening with low compound consumption and cover the most commonly faced toxicity related challenges.</p> <ul class="wp-block-list"> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-toxicology/#Cardiotoxicity_Screening">Cardiotoxicity screening</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-toxicology/#Cardiotoxicity_Screening">hERG Predictor fluorescence polarisation assay</a></li> <li class="has-medium-font-size">Electrophysiology (via our partner <a href="https://axxam.com/" target="_blank" rel="noreferrer noopener">Axxam</a>)</li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-toxicology/#Genotoxicity_Screening">Genotoxicity screening</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-toxicology/#Cytotoxicity_Screening">Cytotoxicity screening</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-toxicology/#Mechanistic_Toxicity_Assays">Mechanistic toxicity assays</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-toxicology/#Hematologic_toxicology">Hematologic toxicity</a></li> <li class="has-medium-font-size"><a href="https://admescope.com/services/in-vitro-toxicology/#Hepatotoxicity_screening">Hepatoxicity and drug induced liver injury assessment</a></li> </ul> <div style="height:10px" aria-hidden="true" class="wp-block-spacer"></div> <div style="height:30px" aria-hidden="true" class="wp-block-spacer"></div> <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" /> <h2 class="wp-block-heading"><span class="ez-toc-section" id="In_vivo_drug_metabolism_and_pharmacokinetics"></span><em>In vivo</em> drug metabolism and pharmacokinetics<span class="ez-toc-section-end"></span></h2> <figure class="wp-block-image alignright size-full"><img decoding="async" width="336" height="386" src="data:image/svg+xml,%3Csvg%20xmlns='http://www.w3.org/2000/svg'%20viewBox='0%200%20336%20386'%3E%3C/svg%3E" alt="" class="wp-image-2307" data-lazy-srcset="https://symeres.com/wp-content/uploads/2023/05/adme-tox-2.png 336w, https://symeres.com/wp-content/uploads/2023/05/adme-tox-2-261x300.png 261w" data-lazy-sizes="(max-width: 336px) 100vw, 336px" data-lazy-src="https://symeres.com/wp-content/uploads/2023/05/adme-tox-2.png" /><noscript><img decoding="async" width="336" height="386" src="https://symeres.com/wp-content/uploads/2023/05/adme-tox-2.png" alt="" class="wp-image-2307" srcset="https://symeres.com/wp-content/uploads/2023/05/adme-tox-2.png 336w, https://symeres.com/wp-content/uploads/2023/05/adme-tox-2-261x300.png 261w" sizes="(max-width: 336px) 100vw, 336px" /></noscript></figure> <ul class="wp-block-list"> <li class="has-medium-font-size">The <a href="https://www.admescope.com/services/in-vivo-dmpk/"><em>in vivo</em> DMPK services</a> cover a variety of animal experiments in several species. In-house rodent PK studies are carried out in AAALAC accredited animal facilities and studies with other species are completed together with selected European in-life partners.</li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vivo-dmpk/#Animal_Pharmacokinetics">Animal pharmacokinetics</a></li> <li class="has-medium-font-size"><a href="https://www.admescope.com/services/in-vitro-metabolism/#Metabolite_Identification_and_Profiling"><em>In vivo</em> MetID</a></li> </ul> <div style="height:10px" aria-hidden="true" class="wp-block-spacer"></div> <div style="height:30px" aria-hidden="true" class="wp-block-spacer"></div> <hr class="wp-block-separator has-alpha-channel-opacity is-style-wide" /> <h2 class="wp-block-heading" id="anchor"><span class="ez-toc-section" id="Safety_metabolism_and_in_vivo_MetID"></span>Safety metabolism and <em>in vivo</em> MetID<span class="ez-toc-section-end"></span></h2> <p class="has-medium-font-size"><a href="https://www.admescope.com/services/safety-metabolism/">Safety metabolism</a> studies help you to confirm that the exposure to human metabolites is adequate in preclinical safety species, or to effectively identify potential MIST (metabolites in safety testing) issues in time, through a battery of different types of <em>in vivo</em> MetID studies.</p> <ul class="wp-block-list"> <li class="has-medium-font-size">Metabolite profiling and characterisation in pre-clinical species</li> <li class="has-medium-font-size">Human metabolite profiling and characterisation (FIM, SAD, MAD)</li> <li class="has-medium-font-size">Human MIST analysis (MAD + preclinical safety species)</li> <li class="has-medium-font-size">Metabolite profiling and characterisation in radiolabelled human ADME study</li> <li class="has-medium-font-size">Metabolite profiling in milk secretion studies</li> </ul> <div style="height:47px" aria-hidden="true" class="wp-block-spacer"></div> </div></div> <section class="block block--primary"> <div class="block__content block__content--right"> <div class="block__text"> <h2>Feel free to contact us!</h2> <p><strong>Curious to know more about what can we do for you? 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class="downloads__files"> <h3>Files</h3> <div> <ul></ul> </div> <button style="margin-top:20px;" id="remove-all-files" type="submit" class="button">Remove all</button> </div> <form class="downloads__form form" action="https://symeres.com/wp-admin/admin-ajax.php" method="POST" id="actualsymeresdownloads"> <p>Please, provide us your email address so that we can send you a link for downloading the requested files.</p> <div class="form__row"> <div class="form__col"> <label for="first-name">First name</label> <input id="first-name" name="first-name" type="text" placeholder="First name" required> </div> <div class="form__col"> <label for="last-name">Last name</label> <input id="last-name" name="last-name" type="text" placeholder="Last name" required> </div> </div> <div class="form__row"> <div class="form__col"> <label for="company">Company</label> <input id="company" name="company" type="text" placeholder="Company" required> </div> </div> <div class="form__row"> <div class="form__col"> <label for="email">Corporate email</label> <input id="email" name="email" type="email" placeholder="Corporate email" required> </div> </div> <div class="form__row"> <div class="form__col"> <label for="agreement"> <input id="agreement" name="agreement" type="checkbox" required> <div>By downloading, I agree to the <a href='/privacy-policy/'>privacy policy</a></div> </label> </div> </div> <div class="form__row"> <div class="form__col"> <input type="text" name="downloaded_files" value="" style="opacity: 0;height: 0;overflow: hidden;"> <button type="submit" class="button button--primary">Download file(s)</button> <input type="hidden" name="action" value="symeresdownloads"> </div> </div> </form> </div> </section><script type="rocketlazyloadscript">window.addEventListener('DOMContentLoaded', function() { jQuery( document ).ready(function() { jQuery(function ($) { let downloads = {}; $('body').on('click', '#downloads-close', function(){ $('.downloads__label').css('display', 'flex'); $('.downloads__content').css('display', 'none'); }); $('body').on('click', '.downloads__label', function(){ $('.downloads__label').css('display', 'none'); $('.downloads__content').css('display', 'flex'); }); $('body').on('change', 'form.downloads', function(){ let downloadsList = ''; let filenames = {}; $('input:checkbox[name=download]').each(function(){ filenames[$(this).data('filename')] = $(this).data('filetitle'); if (this.checked) { downloads[$(this).data('download')] = $(this).data('filename'); } else { if ($(this).data('download') in downloads) { delete downloads[$(this).data('download')]; } if (localStorage.getItem('downloads')) { let downloadsFromLocalStorage = JSON.parse(localStorage.getItem('downloads')); if ($(this).data('download') in downloadsFromLocalStorage) { delete downloadsFromLocalStorage[$(this).data('download')]; localStorage.setItem('downloads', JSON.stringify(downloadsFromLocalStorage)); } } } $('input[name="downloaded_files"]').val(Object.values(filenames).join(',')); }); // set filenames + titles in localStorage if (Object.keys(filenames).length) { let filenamesJson = JSON.stringify(filenames); if (localStorage.getItem('filenames')) { let currentFilenames = JSON.parse(localStorage.getItem('filenames')); filenames = { ...currentFilenames, ...filenames }; filenamesJson = JSON.stringify(filenames); } localStorage.setItem('filenames', filenamesJson); } if (Object.keys(downloads).length) { $('.downloads__aside').css('display', 'block'); let downloadsJson = JSON.stringify(downloads); if (localStorage.getItem('downloads')) { let currentDownloads = JSON.parse(localStorage.getItem('downloads')); downloads = { ...currentDownloads, ...downloads }; downloadsJson = JSON.stringify(downloads); } localStorage.setItem('downloads', downloadsJson); } else { if (!localStorage.getItem('downloads')) { localStorage.removeItem('downloads'); } } Object.keys(downloads).forEach(key => { let label = $('.downloads li label[for="download-file-' + downloads[key] + '"]').text(); if (localStorage.getItem('downloads')) { let downloadsFromLocalStorage = JSON.parse(localStorage.getItem('downloads')); if (localStorage.getItem('filenames')) { let filenames = JSON.parse(localStorage.getItem('filenames')); if (downloadsFromLocalStorage[key] in filenames) { label = filenames[downloadsFromLocalStorage[key]]; } } if (label === '') { label = $('.downloads li label[for="download-file-' + downloadsFromLocalStorage[key] + '"]').text(); } } downloadsList += '<li><button data-download="' + key + '"><svg class="downloads__delete"><use xlink:href="#icon-times"></use></svg></button><span><svg class="downloads__icon"><use xlink:href="#icon-download-file"></use></svg></span>' + label.trim() + '</li>'; }); $('.downloads__label span').text(Object.keys(downloads).length); $('#selected-files ul').html(downloadsList); // if (Object.keys(downloads).length) { //if (localStorage.getItem('downloads')) { // $('.downloads__aside').css('display', 'block'); // } else { // $('.downloads__aside').css('display', 'none'); // } }); if (localStorage.getItem('downloads')) { let downloadsFromLocalStorage = JSON.parse(localStorage.getItem('downloads')); let downloadsList = ''; $("input[name='downloaded_files']").val(Object.values(downloadsFromLocalStorage).join(',')); Object.keys(downloadsFromLocalStorage).forEach(key => { $(".downloads ul").find("[data-filename='" + downloadsFromLocalStorage[key] + "']").prop('checked', true); let label = ''; if (localStorage.getItem('filenames')) { let filenames = JSON.parse(localStorage.getItem('filenames')); if (downloadsFromLocalStorage[key] in filenames) { label = filenames[downloadsFromLocalStorage[key]]; } } if (label === '') { label = $('.downloads li label[for="download-file-' + downloadsFromLocalStorage[key] + '"]').text(); } downloadsList += '<li><button data-download="' + key + '"><svg class="downloads__delete"><use xlink:href="#icon-times"></use></svg></button><span><svg class="downloads__icon"><use xlink:href="#icon-download-file"></use></svg></span>' + label.trim() + '</li>'; }); $('.downloads__label span').text(Object.keys(downloadsFromLocalStorage).length); $('#selected-files ul').html(downloadsList); $('.downloads__aside').css('display', 'block'); } else { $('.downloads__aside').css('display', 'none'); } $('body').on('click', '#remove-all-files', function(){ localStorage.removeItem('downloads'); $('#selected-files div ul li').remove(); $('.downloads__aside').css('display', 'none'); location.reload(); }); $('body').on('click', '#selected-files button', function(){ $('form.downloads input[data-download=' + $(this).data('download') + ']').prop('checked', false).trigger('change'); if (localStorage.getItem('downloads')) { let downloadsLocalObj = JSON.parse(localStorage.getItem('downloads')); if ($(this).data('download') in downloadsLocalObj) { delete downloadsLocalObj[$(this).data('download')]; 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