{"id":109,"date":"2019-04-24T12:39:34","date_gmt":"2019-04-24T12:39:34","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=109"},"modified":"2020-09-04T03:20:25","modified_gmt":"2020-09-04T03:20:25","slug":"hepaticclearance","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/hepaticclearance\/","title":{"rendered":"Hepatic Clearance"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">&#8220;Part of the total <a href=\"\/pharmacology\/clearance\">clearance<\/a> due to liver enzyme activity and biliary excretion&#8221;<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>Hepatic clearance quantifies the loss of drug during its passage through the liver. Hepatic clearance results from hepatic <a href=\"\/pharmacology\/metabolism\">metabolism<\/a> and <a href=\"\/pharmacology\/biliary-excretion\">biliary excretion<\/a>\n and is a function of the hepatic blood flow, the drug plasma protein \nbinding and the activity of liver enzymes and transporters. Variation of\n one of these parameters may more or less influence the hepatic \nclearance of a drug, depending on its hepatic <a href=\"\/pharmacology\/extractionratio\">extraction ratio<\/a>.\n<\/p>\n\n\n\n<p>Variation of liver enzyme activity mainly affects the hepatic <a href=\"\/pharmacology\/extractionratio\">intrinsic clearance<\/a> (CLint). This is the main source of interindividual variation of hepatic clearance.\n<\/p>\n\n\n\n<p>Oral bioavailability is related to the hepatic \nextraction ratio. The higher the extraction ration, the higher the \nhepatic first past effect and the lower the bioavailability.<\/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\/hepaticlcearance_Trim.mp4\"><\/video><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>If the liver is the most important organ for the \nelimination of a drug, it is essential to know whether the drug has a \nhigh or low hepatic <a href=\"\/pharmacology\/extractionratio\">extraction ratio<\/a>: it determines dosage adaptations in patients presenting conditions altering:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>hepatic blood flow (e.g. congestive heart failure)<\/li><li>plasma protein binding (e.g. hypoalbuminemia, displacement by other drugs) <\/li><li>hepatic enzymatic activity (e.g. liver failure, specific inhibition or induction by drugs, genetic polymorphism)<\/li><\/ol>\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 e = 0.3;\n        \n        let q = 1;\n        \n        let otherCl = 2;\n\n        let ka = 1.5;\n        let tH;\n\n        const maxTime = 100;\n\n        function getPlasmaConcentration(h) {\n            let formulaPlasmaConcentration = (dose*f*ka\/(vd*(ka-cl\/vd))*(Math.exp(-cl\/vd*h)));\n            \n            formulaPlasmaConcentration = (dose*(1-e)*ka\/(vd*(ka-q*e\/vd))*(Math.exp(-1*(q+otherCl)*h\/vd)-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-q\" ).slider( \"option\", \"value\", q);\n            $( \"#slider-e\" ).slider( \"option\", \"value\", e);\n            chart.update();\n        }\n\n        let sliderQ = '<div id=\"slider-q\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-q\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">Q<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderQ);\n\nlet sliderE = '<div id=\"slider-e\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-e\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">E<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderE);\n\n\n   \n\n        $(function() {\n\n            let handleQ = $('#custom-handle-q');\n\n            $( \"#slider-q\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0.1,\n                max: 2,\n                step: 0.1,\n                value: q,\n                create: function() {\n                    handleQ.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    q = ui.value;\n                    handleQ.text( ui.value );\n                    updateSlider();\n                }\n            });\n\n            let handleE = $('#custom-handle-e');\n\n            $( \"#slider-e\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0.01,\n                max: 1,\n                step: 0.01,\n                value: e,\n                create: function() {\n                    handleE.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    e = ui.value;\n                    handleE.text( ui.value );\n                    updateSlider();\n                }\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>Extrarenal fraction (Qo): fraction of the drug \nthat is not eliminated by unchanged renal excretion (i.e. most commonly \nthrough hepatic metabolism). Qo = 1 - <a href=\"\/pharmacology\/renalclearance\">the fraction excreted (fe<\/a>).<\/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\">$$CL_{hep} = Q * E$$<\/p><p class=\"formula\"><\/div>\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\">$$F = 1 - E$$<\/p><p class=\"formula\"><\/div>\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\">$$Q_o = {CL_{hep} \\over CL_{total}}$$<\/p><p class=\"formula\"><\/div>\n\n\n\n<p><strong>F<\/strong> = bioavailability <\/p>\n\n\n\n<p><strong>CL hep<\/strong> = hepatic clearance <\/p>\n\n\n\n<p><strong>CL total<\/strong> = <a href=\"\/pharmacology\/clearance\">total Clearance<\/a> <\/p>\n\n\n\n<p><strong>Q0<\/strong> = extrarenal fraction <\/p>\n\n\n\n<p><strong>Q<\/strong> = hepatic perfusion <\/p>\n\n\n\n<p><strong>E<\/strong> = <a href=\"\/pharmacology\/extractionratio\">extraction ratio<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Part of the total clearance due to liver enzyme activity and biliary excretion&#8221; Description Hepatic clearance quantifies the loss of drug during its passage through the liver. Hepatic clearance results from hepatic metabolism and biliary excretion and is a function of the hepatic blood flow, the drug plasma protein binding and the activity of liver &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/hepaticclearance\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Hepatic 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-109","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/109","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=109"}],"version-history":[{"count":18,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/109\/revisions"}],"predecessor-version":[{"id":1300,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/109\/revisions\/1300"}],"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=109"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}