{"id":107,"date":"2019-04-24T12:39:34","date_gmt":"2019-04-24T12:39:34","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=107"},"modified":"2020-09-04T03:14:21","modified_gmt":"2020-09-04T03:14:21","slug":"clearance","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/clearance\/","title":{"rendered":"Clearance"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\"> &#8220;Rate of drug elimination divided by plasma concentration, giving a  volume of plasma from which drug is completely removed per unit of  time&#8221;<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>Clearance reflects the elimination of the drug from the body. This drug elimination generally results from liver <a href=\"\/pharmacology\/metabolism\">metabolism<\/a> and\/or <a href=\"\/pharmacology\/excretion\">excretion<\/a> by the kidneys. <\/p>\n\n\n\n<div class=\"wp-block-columns has-2-columns is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p>\nIn order to be eliminated, a drug must be presented  to the organs of \nelimination by the plasma flow. The higher the drug  concentration, the \nmore drug is presented to the organs and thus can be  eliminated. In \nother words, the rate of drug elimination is proportional  to the plasma\n concentration. Clearance is precisely this coefficient of  \nproportionality. By contrast, the fraction of drug that is eliminated  \nremains constant. Clearance of most drugs, for which excretion and  \nmetabolism are not saturated, is constant over the range of doses  \nencountered clinically. Such drugs are said to undergo first order  \nkinetics.\n\n<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-video\"><video height=\"346\" style=\"aspect-ratio: 346 \/ 346;\" width=\"346\" controls src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/05\/clearance.mp4\"><\/video><\/figure>\n<\/div>\n<\/div>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>Clearance is the only factor determining the average drug concentration after the <a href=\"\/pharmacology\/intravenous-bolus\">iv injection<\/a> of a given dose. After an <a href=\"\/pharmacology\/extravascular-administration\">extravascular<\/a> administration, the average drug exposure is determined both by clearance and by <a href=\"\/pharmacology\/bioavailability\">bioavailability<\/a>. In a <a href=\"\/pharmacology\/repeated-administration\">multiple dosage regimen<\/a>,\n establishing the value of clearance is necessary to predict an average \ndrug concentration within a therapeutic window. The individual factors \nthat can influence clearance are the intrinsic functions of liver or \nkidneys. Therefore, variation of clearance can be anticipated when there\n is a major impairment of these organs. Blood flow to the organs of \nelimination can also affect clearance.<\/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\n           let formulaPlasmaConcentration = (dose*f*ka\/(vd*(ka-cl\/vd))*(Math.exp(-cl\/vd*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\", cl);\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=\"\">CL<\/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: 0.5,\n                max: 30,\n                step: 0.1,\n                value: cl,\n                create: function() {\n                    handle.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    cl = 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\">Related terms<\/h3>\n\n\n\n<p>For every drug, each organ of elimination has its own clearance (e.g. <a href=\"\/pharmacology\/hepaticclearance\">hepatic clearance<\/a>, <a href=\"\/pharmacology\/renalclearance\">renal clearance<\/a>). The total body clearance results from the addition of these clearances:\n<\/p>\n\n\n\n<p><strong>CL<\/strong>= <a href=\"\/pharmacology\/renalclearance\">Renal CL<\/a>+ <a href=\"\/pharmacology\/hepaticclearance\">Hepatic CL<\/a>+ other CL<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Assessment<\/h3>\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\">$$CL = \\lambda * Vd$$<\/p><p class=\"formula\"><\/div>\n\n\n\n<p> <strong>\u03bb<\/strong>  =<a href=\"\/pharmacology\/halflife\"> Elimination rate constant<\/a> <\/p>\n\n\n\n<p><strong>Vd<\/strong> = <a href=\"\/pharmacology\/volumeofdistribution\">Volume of distribution<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Rate of drug elimination divided by plasma concentration, giving a volume of plasma from which drug is completely removed per unit of time&#8221; Description Clearance reflects the elimination of the drug from the body. This drug elimination generally results from liver metabolism and\/or excretion by the kidneys. In order to be eliminated, a drug must &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/clearance\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Clearance&#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-107","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/107","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=107"}],"version-history":[{"count":30,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/107\/revisions"}],"predecessor-version":[{"id":1296,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/107\/revisions\/1296"}],"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=107"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}