{"id":146,"date":"2019-04-24T12:51:40","date_gmt":"2019-04-24T12:51:40","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=146"},"modified":"2020-09-04T03:39:20","modified_gmt":"2020-09-04T03:39:20","slug":"extravascular-administration","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/profiles\/extravascular-administration\/","title":{"rendered":"Extravascular Administration"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\"> &#8220;Drug administration by any other route than the intravenous route&#8221; <\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>After extravascular drug administration, the rate\n and extent of drug absorption, from its site of administration to the \nsystemic circulation, determine the onset and the intensity of drug \neffect. The duration of effect is mainly determined by the dose, the \nhalf-life and to a variable degree by the absorption rate (e.g. \nslow-release formulations).\n<\/p>\n\n\n\n<p>Initially, after an extravascular administration, \nthe entire drug is at the site of absorption and none has yet reached \nthe systemic circulation. Therefore, the rate of absorption is high and \nthere is no elimination yet. As long as the rate of absorption exceeds \nthat of elimination, the plasma concentration rises (absorption phase). \nThe maximum concentration (Cmax) is reached when the rate of disposition\n matches the rate of absorption. Thereafter, the rate of disposition \nexceeds the rate of absorption and the plasma concentration declines \n(disposition phase).\n<\/p>\n\n\n\n<p>The factors affecting the plasma concentration-time profile after extravascular administration are:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Dose: Lower doses usually produce a proportional decrease in plasma concentration at all times.<\/li><li>Bioavailability: lower bioavailability results in a proportional decrease in plasma concentration. <\/li><li>Rate of absorption: Slower rate of absorption delays and reduces the magnitude of the peak of plasma concentration.<\/li><li>Volume\n of distribution: Larger Vd is responsible for both a lower peak \nconcentration and a longer elimination half-life, delaying the peak \napproach.<\/li><li>Clearance: CL mainly affects the disposition phase; \nhowever, an increase in clearance also results in a faster approach to a\n lower peak concentration.<\/li><\/ol>\n\n\n\n<figure class=\"wp-block-video aligncenter\"><video height=\"336\" style=\"aspect-ratio: 334 \/ 336;\" width=\"334\" autoplay controls loop src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/07\/extravascularadministration_Trim.mp4\"><\/video><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>Extravascular administration is convenient, \nrelatively safe and economical. It is however not feasible for a range \nof drugs destroyed before their absorption, insoluble or with poor \ndigestive tolerability. The progressive absorption of the drug limits \nand delays the peak of blood concentration. \n<\/p>\n\n\n\n<p>The extravascular dose must be adapted to the \nbioavailability and sometimes to the absorption rate of the drug. \nVariation of the rate of absorption and bioavailability can add to the \nglobal pharmacokinetic variability, particularly in patients with \ndiseases affecting the absorption site (e.g. affections of the \ngastro-intestinal tract).<\/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 = 500;\n        let baseDose = 500;\n\n        let mDose = 500;\n        let baseMDose = 500;\n\n        let tau = 12;\n        let baseTau = 12;\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 = 2        \n        let tH;\n        \n        let rr = 1.5;\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-dose\" ).slider( \"option\", \"value\", dose);\n            $( \"#slider-rr\" ).slider( \"option\", \"value\", rr);\n            chart.update();\n        }\n\n        let sliderDose = '<div id=\"slider-dose\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-dose\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">LD<\/span>' +\n                        '<\/div>';\n        \n        let sliderRr = '<div id=\"slider-rr\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-rr\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">RR<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderDose);\n        $('#divSliderContainer').append(sliderRr);\n\n        $(function() {\n\n            let handleDose = $('#custom-handle-dose');\n\n            $( \"#slider-dose\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0,\n                max: 1000,\n                step: 10,\n                value: dose,\n                create: function() {\n                    handleDose.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    dose = ui.value;\n                    handleDose.text( ui.value );\n                    updateSlider();\n                }\n            });\n\n            let handleRr = $('#custom-handle-rr');\n\n            $( \"#slider-rr\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0.1,\n                max: 3,\n                step: 0.1,\n                value: rr,\n                create: function() {\n                    handleRr.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    rr = ui.value;\n                    handleRr.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<p><strong>RR<\/strong> = Release rate<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Related terms<\/h3>\n\n\n\n<p>tmax: tmax is the time required to reach the maximum plasma concentration (Cmax).\n<\/p>\n\n\n\n<p>Lag time: A lag time is a delay between drug \nadministration and the beginning of drug absorption. This may be due to \nformulation (e.g. coated tablets), or to physiological factors (e.g. \ngastric emptying).\n<\/p>\n\n\n\n<p><a href=\"\/pharmacology\/absorptionrateconstant\">Absorption rate constant<\/a> (ka)\n<\/p>\n\n\n\n<p><a href=\"\/pharmacology\/absorptionrateconstant\">Controlled-release<\/a> formulations <\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Assessment<\/h3>\n\n\n\n<p>The drug plasma concentration time profile can be described by the following equation (Bateman's formula):\n<\/p>\n\n\n\n<div class=\"wp-block-blocks-latex-block-latex\">$$F={F*D*\\color{pink}{ka} \\over Vd*(\\color{pink}{ka}-\\color{RoyalBlue}{\\lambda})}*{(e^{-\\color{RoyalBlue}{\\lambda}*t}}-e^{-\\color{pink}{ka}*t)}$$  <p class=\"formula\"><\/div>\n\n\n\n<p><strong>ka<\/strong> = absorption rate constant <\/p>\n\n\n\n<p> <strong>\u03bb<\/strong> = <a href=\"\/pharmacology\/halflife\">elimination constant rate<\/a> = CL\/Vd <\/p>\n\n\n\n<p><strong>CL<\/strong> = clearance <\/p>\n\n\n\n<p><strong>F<\/strong> = <a href=\"\/pharmacology\/bioavailability\">bioavailability<\/a> <\/p>\n\n\n\n<p><strong>D<\/strong> = dose <\/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;Drug administration by any other route than the intravenous route&#8221; Description After extravascular drug administration, the rate and extent of drug absorption, from its site of administration to the systemic circulation, determine the onset and the intensity of drug effect. The duration of effect is mainly determined by the dose, the half-life and to a &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/profiles\/extravascular-administration\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Extravascular Administration&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":8,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-146","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/146","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=146"}],"version-history":[{"count":20,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/146\/revisions"}],"predecessor-version":[{"id":1319,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/146\/revisions\/1319"}],"up":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/8"}],"wp:attachment":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/media?parent=146"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}