{"id":108,"date":"2019-04-24T12:39:34","date_gmt":"2019-04-24T12:39:34","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=108"},"modified":"2020-09-04T03:18:36","modified_gmt":"2020-09-04T03:18:36","slug":"extractionratio","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/extractionratio\/","title":{"rendered":"Extraction Ratio"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\"> &#8220;Rate of plasma drug removal by an organ of elimination, divided by the rate at which it is presented to this organ&#8221;<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>The extraction ratio of an organ of elimination \n(e.g. the liver or the kidneys) can be viewed as the measure of the \norgan&#8217;s relative efficiency in eliminating the drug from the systemic \ncirculation over a single pass through the organ. The extraction ratio \nmay range from 0 to 1. An extraction ration close to 0 indicates that \nmost of the drug escapes elimination during a single pass through the \norgan. An extraction ratio close to 1 indicates that most of the drug is\n eliminated during a single pass through the organ.\n<\/p>\n\n\n\n<figure class=\"wp-block-video aligncenter\"><video height=\"346\" style=\"aspect-ratio: 346 \/ 346;\" width=\"346\" autoplay controls loop src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/06\/extractionratio_Trim.mp4\"><\/video><\/figure>\n\n\n\n<p>The organ clearance (mainly the <a href=\"\/pharmacology\/hepaticclearance\">hepatic<\/a> or the <a href=\"\/pharmacology\/renalclearance\">renal clearance<\/a>)\n may be influenced by the organ blood flow, protein binding and the \nintrinsic ability of the organ to eliminate the drug. The extent of this\n influence depends on the extraction ratio of the drug:\n<\/p>\n\n\n\n<p>1) Variation of organ blood flow:\n<\/p>\n\n\n\n<p>a) for drugs with low extraction ratio (&lt;0.3): \nthe venous drug concentration is virtually identical to the arterial \nconcentration and organ clearance is poorly influenced by blood flow \nvariations.\n<\/p>\n\n\n\n<p>b) for drugs with high extraction ratio (&gt;0.7): \nchanges in blood flow produce corresponding changes in clearance, e.g. \nan increase in organ blood flow will increase the amount of drug \npresented to and eliminated by the organ.\n<\/p>\n\n\n\n<p>2) Variation of plasma protein binding:\n<\/p>\n\n\n\n<p>a) for drugs with low extraction ratio: only unbound\n drug penetrates membranes and is available for elimination. An increase\n of the unbound fraction will thus proportionally increase the \nclearance. Therefore, the unbound drug concentration remains constant \nand no adaptation of the dosage regimen is required.\n<\/p>\n\n\n\n<p>b) for drugs with high extraction ratio: the organ \nis capable of removing all the drug presented to it, independently of \nplasma binding. Therefore, even if the fraction of unbound drug \nincreases, the clearance remains constant and the unbound concentration \nthen increases and may lead to toxicity.\n<\/p>\n\n\n\n<p>3) Variation of the organ&#8217;s intrinsic ability to eliminate the drug:\n<\/p>\n\n\n\n<p>a) for drugs with low extraction ratio: a slight change in this ability will affect organ clearance. \n<\/p>\n\n\n\n<p>b) for drugs with high extraction ratio: this \nability is so elevated that this variation poorly influence clearance, \nwhich is mainly limited by organ blood flow.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>When a drug is mainly eliminated by the liver or \nby the kidney, it is essential to know the extraction ratio of the drug \nthrough this organ to be able to evaluate which conditions affecting the\n organ will change the clearance and to further adapt the dosage \nregimen.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Related terms<\/h3>\n\n\n\n<p>Intrinsic clearance (CLint): theoretical \nunrestricted maximum clearance of unbound drug by an eliminating organ, \nin absence of blood flow or plasma protein binding limitations. This \nterm relates to the functional reserve of the organ. The CLint may be \ndetermined in vitro using enzyme kinetics.<\/p>\n\n\n\n<p><p class=\"hiddenTitle\">Chart Pharmacokinetics<\/p>\n<div>\n\n    <div id=\"chartContainer\">\n        <canvas id=\"chart\"><\/canvas>\n        <div class=\"\" id=\"divSliderContainer\"><\/div>\n    <\/div>\n\n    <script>\n\n        let chart;\n        let baseDataChartValues = [];\n        let dataChart = [];\n        let dataChartStoredValues = [];\n        let labelsChart = [];\n\n        let dose = 1000;\n        let baseDose = 1000;\n\n        let mDose = 1000;\n        let baseMDose = 1000;\n\n        let tau = 6;\n        let baseTau = 6;\n\n        let vd = 50;\n        let baseVd = 50;\n\n        let cl = 10;\n        let baseCl = 10;\n\n        let f = 0.7;\n        let baseF = 0.7;\n\n        let ka = 1.5;\n        let tH;\n\n        const maxTime = 20;\n\n        function getPlasmaConcentration(h) {\n            let formulaPlasmaConcentration = (dose*f*ka\/(vd*(ka-cl\/vd))*(Math.exp(-cl\/vd*h)-Math.exp(-ka*h)));\n\n            return formulaPlasmaConcentration;\n        }\n\n        \/*\n         *\n         * t1\/2 = ln(2) * (volume of distribution \/ clearance)\n         *\n         *\/\n        function getHalfLife() {\n            tH = Math.log(2)*(vd\/cl);\n            return (Math.round(tH * 100) \/ 100);\n        }\n\n        function updateSlider(updateStored = false) {\n            dataChart = [];\n            if(updateStored) dataChartStoredValues = [];\n\n            for(let i = 0; i <= maxTime; i++) {\n                let concentration = getPlasmaConcentration(i);\n                dataChart.push(concentration);\n                if(updateStored) dataChartStoredValues.push(concentration);\n            }\n\n            chart.data.datasets[0].data = dataChart;\n            chart.data.datasets[1].data = dataChartStoredValues;\n\n            $( \"#slider-f\" ).slider( \"option\", \"value\", ka);\n            chart.update();\n        }\n\n        let sliderF = '<div id=\"slider-f\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-f\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">Ka<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderF);\n\n\n   \n\n        $(function() {\n\n            let handle = $('#custom-handle-f');\n\n            $( \"#slider-f\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0.1,\n                max: 3,\n                step: 0.01,\n                value: ka,\n                create: function() {\n                    handle.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    ka = ui.value;\n                    handle.text( ui.value );\n                    updateSlider();\n                }\n            });\n        });\n\n        Chart.pluginService.register({\n            beforeInit: function(chart) {\n\n                for(let i = 0; i <= maxTime; i++) {\n                    labelsChart.push(i);\n                    dataChart.push(getPlasmaConcentration(i));\n\n                    dataChartStoredValues = dataChart;\n                    baseDataChartValues = dataChart;\n                }\n\n            }\n        });\n\n        chart = new Chart(document.getElementById(\"chart\"), {\n            type: 'line',\n            data: {\n                labels: labelsChart,\n                datasets: [{\n                    label: \"Plasma Concentration\",\n                    data: dataChart,\n                    borderColor: colorDatasetMain.borderColor,\n                    fillColor: colorDatasetMain.fillColor,\n                    strokeColor: colorDatasetMain.strokeColor,\n                    highlightFill: colorDatasetMain.highlightFill,\n                    highlightStroke: colorDatasetMain.highlightStroke,\n                    borderWidth: \"1\",\n                    pointRadius: 0,\n                    fill: false\n                }, {\n                    label: \"Plasma Concentration\",\n                    data: dataChartStoredValues,\n                    borderColor: colorDatasetStored.borderColor,\n                    fillColor: colorDatasetStored.fillColor,\n                    strokeColor: colorDatasetStored.strokeColor,\n                    highlightFill: colorDatasetStored.highlightFill,\n                    highlightStroke: colorDatasetStored.highlightStroke,\n                    borderWidth: \"1\",\n                    pointRadius: 0,\n                    fill: false\n                }]\n            },\n            options: {\n                scales: {\n                    xAxes: [{\n                        scaleLabel: {\n                            display: true,\n                            labelString: 'H [hour]'\n                        }\n                    }],\n                    yAxes: [{\n                        scaleLabel: {\n                            display: true,\n                            labelString: 'C [mg\/l]'\n                        }\n                    }]\n                },\n                responsive: true,\n                maintainAspectRatio: false\n            }\n        });\n\n    <\/script>\n\n<\/div><\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Assessment<\/h3>\n\n\n\n<p>The extraction ratio can be assessed by using the\n following formula which relates the rate of elimination of the drug to \nits rate of presentation to the organ of elimination. This requires \nsampling of arterial and venous blood at organ outflow.\n<\/p>\n\n\n\n<div class=\"wp-block-blocks-latex-block-latex\"><script type=\"text\/x-mathjax-config\">   MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]}}); <\/script> <p class=\"formula\">$$E = {\\color{pink}{C_A}-\\color{RoyalBlue}{C_V} \\over \\color{pink}{C_A}}$$<\/p><\/div>\n\n\n\n<p>Supposing that there is an instantaneous and \ncomplete mixing of the drug with the organ tissues, the following \nequation may be used, integrating CLint and fub obtained in vitro and \nthe in vivo blood flow measured through the organ:\n<\/p>\n\n\n\n<div class=\"wp-block-blocks-latex-block-latex\"><script type=\"text\/x-mathjax-config\">   MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]}}); <\/script> <p class=\"formula\">$$E = {\\color{pink}{fub} *\\color{RoyalBlue}{CLint} \\over Q +(\\color{pink}{fub} * \\color{RoyalBlue}{CLint})}$$<\/p><p class=\"formula\"><\/div>\n\n\n\n<p><strong>E<\/strong>         = extraction ratio <\/p>\n\n\n\n<p><strong>CA<\/strong>     = arterial drug concentration <\/p>\n\n\n\n<p><strong>CV<\/strong>      = venous drug concentration <\/p>\n\n\n\n<p><strong>fub<\/strong>     = fraction of unbound drug  <\/p>\n\n\n\n<p><strong>Q<\/strong>         = blood flow to the organ <\/p>\n\n\n\n<p><strong>CLint<\/strong> = intrinsic clearance<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Rate of plasma drug removal by an organ of elimination, divided by the rate at which it is presented to this organ&#8221; Description The extraction ratio of an organ of elimination (e.g. the liver or the kidneys) can be viewed as the measure of the organ&#8217;s relative efficiency in eliminating the drug from the systemic &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/extractionratio\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Extraction Ratio&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":7,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-108","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/108","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/comments?post=108"}],"version-history":[{"count":23,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/108\/revisions"}],"predecessor-version":[{"id":1299,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/108\/revisions\/1299"}],"up":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/7"}],"wp:attachment":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/media?parent=108"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}