{"id":152,"date":"2019-04-24T12:53:35","date_gmt":"2019-04-24T12:53:35","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=152"},"modified":"2020-09-04T03:53:38","modified_gmt":"2020-09-04T03:53:38","slug":"population-pharmacokinetics","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/profiles\/population-pharmacokinetics\/","title":{"rendered":"Population Pharmacokinetics"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">\n&#8220;Study of the extent, sources and correlates of variability in drug pharmacokinetics within a patient population.&#8221;\n\n<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>Certain patient characteristics, such as age, \nbody weight, comorbidity and comedication, can alter the pharmacokinetic\n parameters of a drug. Population pharmacokinetics seeks to assess the \nextent of the variability of these parameters among a patient population\n and to identify the factors that are responsible for such variability.\n<\/p>\n\n\n\n<p>Population pharmacokinetics includes:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Assessment of global variability of the plasma drug concentration profile in a patient population.<\/li><li>Allocation of this variability to pharmacokinetic parameters (e.g. variability of clearance, bioavailability, etc).<\/li><li>Explanation\n of variability by identifying factors of demographic, \npathophysiological, environmental, or concomitant drug-related origin \nthat may influence the pharmacokinetic parameters.<\/li><li>Quantitative estimation of the magnitude of the unexplained variability in the patient population. <\/li><\/ol>\n\n\n\n<p>Sophisticated pharmacostatistical models are needed to analyze population pharmacokinetics.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>Population pharmacokinetics in the drug \ndevelopment process helps identify differences in drug safety and \nefficiency among population subgroups.\n<\/p>\n\n\n\n<p>The mean values of pharmacokinetic parameters allow  the elaboration of the standard dosage regimen of the drug. Variability  that is due to influencal factors leads to dosage adaptation proposed  for patient subsets. Unexplained variability reflects the  reproducibility of pharmacokinetics. This is important because the  efficacy and safety of a drug may decrease as unexplained variability  increases.<\/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 dataChart = [];\n        let baseDataChart = [];\n        let inversedDataChart = [];\n        let labelsChart = [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50];\n\n        let fModifier = 0.1;\n        \n        let chartCl;\n        let dataChartCl = [];\n        let baseDataChartCl = [];\n        let inversedDataChartCl = [];\n \n        let clModifier = 2.5;  \n        \n        let chartVd;\n        let dataChartVd = [];\n        let baseDataChartVd = [];\n        let inversedDataChartVd = [];\n \n        let vDModifier = 5;     \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 = 20;\n        let baseVd = 50;\n\n        let cl = 5;\n        let baseCl = 5;\n\n        let f = 0.5;\n        let baseF = 0.5;\n\n        let ka = 2;\n        let tH;\n        \n        const maxTime = 50;        \n        \n        function getPlasmaConcentration(h, modifiedF) {            \n\n            let formulaPlasmaConcentration = (dose*modifiedF*ka\/(baseVd*(ka-baseCl\/baseVd))*(Math.exp(-baseCl\/baseVd*h)-Math.exp(-ka*h)));\n\n            return formulaPlasmaConcentration;\n        }\n        \n        function getPlasmaConcentrationCl(h, modifiedCl) {\n\n            let formulaPlasmaConcentration = (dose*baseF*ka\/(baseVd*(ka-modifiedCl\/baseVd))*(Math.exp(-modifiedCl\/baseVd*h)-Math.exp(-ka*h)));\n\n            return formulaPlasmaConcentration;\n        }\n        \n        function getPlasmaConcentrationVd(h, modifiedVd) {\n\n            let formulaPlasmaConcentration = (dose*f*ka\/(modifiedVd*(ka-baseCl\/modifiedVd))*(Math.exp(-baseCl\/modifiedVd*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() {\n            dataChart = [];\n            inversedDataChart = [];\n            baseDataChart = [];\n            \n            for(let i = 0; i <= maxTime; i++) {\n\n                let concentration = getPlasmaConcentration(i, f + fModifier);\n                let baseConcentration = getPlasmaConcentration(i, f);\n                let inversedConcentration = getPlasmaConcentration(i, f - fModifier);                \n\n                dataChart.push(concentration);\n                baseDataChart.push(baseConcentration);\n                inversedDataChart.push(inversedConcentration);\n            }\n\n            chart.data.datasets[0].data = dataChart;\n            chart.data.datasets[1].data = baseDataChart;\n            chart.data.datasets[2].data = inversedDataChart;\n\n            $( \"#slider-f\" ).slider( \"option\", \"value\", fModifier);\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=\"\">F<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderF);\n\n        $(function() {\n\n            let handle = $('#custom-handle-f');\n\n            $( \"#slider-f\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0,\n                max: 0.5,\n                step: 0.01,\n                value: fModifier,\n                create: function() {\n                    handle.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    fModifier = 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                            \n                    if(chart.canvas.id == 'chart') {\n                        dataChart.push(getPlasmaConcentration(i, f + fModifier));\n                        baseDataChart.push(getPlasmaConcentration(i, f));\n                        inversedDataChart.push(getPlasmaConcentration(i, f - fModifier));\n                    }\n     \n                    if(chart.canvas.id == 'chartVd') {\n                        dataChartVd.push(getPlasmaConcentrationVd(i, vd + vDModifier));\n                        baseDataChartVd.push(getPlasmaConcentrationVd(i, vd));\n                        inversedDataChartVd.push(getPlasmaConcentrationVd(i, vd - vDModifier));\n                    }\n\n                    if(chart.canvas.id == 'chartCl') { \n                        dataChartCl.push(getPlasmaConcentrationCl(i, cl + clModifier));\n                        baseDataChartCl.push(getPlasmaConcentrationCl(i, cl));\n                        inversedDataChartCl.push(getPlasmaConcentrationCl(i, cl - clModifier));\n                    }\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: baseDataChart,\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                    label: \"Plasma Concentration\",\n                    data: inversedDataChart,\n                    borderColor: colorDatasetBase.borderColor,\n                    fillColor: colorDatasetBase.borderColor,\n                    strokeColor: colorDatasetBase.borderColor,\n                    highlightFill: colorDatasetBase.borderColor,\n                    highlightStroke: colorDatasetBase.borderColor,\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><p class=\"hiddenTitle\">Chart Pharmacokinetics<\/p>\n<div>\n\n    <div id=\"chartContainerCl\" class=\"chartContainer\">\n        <canvas id=\"chartCl\" class=\"chart\"><\/canvas>\n        <div id=\"divSliderContainerCl\" class=\"divSliderContainer\"><\/div>\n    <\/div>\n\n    <script>\n        \n        function updateSliderCl() {\n            dataChartCl = [];\n            inversedDataChartCl = [];\n            baseDataChartCl = [];\n\n            for(let i = 0; i <= maxTime; i++) {\n                let concentration = getPlasmaConcentrationCl(i, cl + clModifier);\n                let baseConcentration = getPlasmaConcentrationCl(i, cl);\n                let inversedConcentration = getPlasmaConcentrationCl(i, cl - clModifier);                \n\n                dataChartCl.push(concentration);\n                baseDataChartCl.push(baseConcentration);\n                inversedDataChartCl.push(inversedConcentration);\n            }\n\n            chartCl.data.datasets[0].data = dataChartCl;\n            chartCl.data.datasets[1].data = baseDataChartCl;\n            chartCl.data.datasets[2].data = inversedDataChartCl;\n\n            $( \"#slider-cl\" ).slider( \"option\", \"value\", clModifier);\n            chartCl.update();\n        }\n\n        let sliderCl = '<div id=\"slider-cl\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-cl\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">CL<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainerCl').append(sliderCl);\n\n        $(function() {\n\n            let handleCl = $('#custom-handle-cl');\n\n            $( \"#slider-cl\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0,\n                max: 2.5,\n                step: 0.1,\n                value: clModifier,\n                create: function() {\n                    handleCl.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    clModifier = ui.value;\n                    handleCl.text( ui.value );\n                    updateSliderCl();\n                }\n            });\n        });\n        \/*\n        Chart.pluginService.register({\n            beforeInit: function(chartCl) {\n  \n                for(let i = 0; i <= maxTime; i++) {\n                    labelsChartCl.push(i);\n                    let concentration = getPlasmaConcentrationCl(i, cl + clModifier);\n                    let baseConcentration = getPlasmaConcentrationCl(i, cl);\n                    let inversedConcentration = getPlasmaConcentrationCl(i, cl - clModifier);                    \n                    \n                    dataChartCl.push(concentration);\n                    baseDataChartCl.push(baseConcentration);\n                    inversedDataChartCl.push(inversedConcentration);\n                }\n\n            }\n        });\n        *\/\n        chartCl = new Chart(document.getElementById(\"chartCl\"), {\n            type: 'line',\n            data: {\n                labels: labelsChart,\n                datasets: [{\n                    label: \"Plasma Concentration\",\n                    data: dataChartCl,\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: baseDataChartCl,\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                    label: \"Plasma Concentration\",\n                    data: inversedDataChartCl,\n                    borderColor: colorDatasetBase.borderColor,\n                    fillColor: colorDatasetBase.borderColor,\n                    strokeColor: colorDatasetBase.borderColor,\n                    highlightFill: colorDatasetBase.borderColor,\n                    highlightStroke: colorDatasetBase.borderColor,\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><p class=\"hiddenTitle\">Chart Pharmacokinetics<\/p>\n<div>\n\n    <div id=\"chartContainerVd\" class=\"chartContainer\">\n        <canvas id=\"chartVd\" class=\"chart\"><\/canvas>\n        <div id=\"divSliderContainerVd\" class=\"divSliderContainer\"><\/div>\n    <\/div>\n\n    <script>\n\n        function updateSliderVd() {\n            dataChartVd = [];\n            inversedDataChartVd = [];\n            baseDataChartVd = [];\n\n            for(let i = 0; i <= maxTime; i++) {\n                let concentration = getPlasmaConcentrationVd(i, vd + vDModifier);\n                let baseConcentration = getPlasmaConcentrationVd(i, vd);\n                let inversedConcentration = getPlasmaConcentrationVd(i, vd - vDModifier);                \n\n                dataChartVd.push(concentration);\n                baseDataChartVd.push(baseConcentration);\n                inversedDataChartVd.push(inversedConcentration);\n            }\n\n            chartVd.data.datasets[0].data = dataChartVd;\n            chartVd.data.datasets[1].data = baseDataChartVd;\n            chartVd.data.datasets[2].data = inversedDataChartVd;\n\n            $( \"#slider-vd\" ).slider( \"option\", \"value\", vDModifier);\n            chartVd.update();\n        }\n\n        let sliderVd = '<div id=\"slider-vd\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-vd\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">VD<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainerVd').append(sliderVd);\n\n        $(function() {\n\n            let handleVd = $('#custom-handle-vd');\n\n            $( \"#slider-vd\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0,\n                max: 10,\n                step: 0.1,\n                value: vDModifier,\n                create: function() {\n                    handleVd.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    vDModifier = ui.value;\n                    handleVd.text( ui.value );\n                    updateSliderVd();\n                }\n            });\n        });\n        \n        chartVd = new Chart(document.getElementById(\"chartVd\"), {\n            type: 'line',\n            data: {\n                labels: labelsChart,\n                datasets: [{\n                    label: \"Plasma Concentration\",\n                    data: dataChartVd,\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: baseDataChartVd,\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                    label: \"Plasma Concentration\",\n                    data: inversedDataChartVd,\n                    borderColor: colorDatasetBase.borderColor,\n                    fillColor: colorDatasetBase.borderColor,\n                    strokeColor: colorDatasetBase.borderColor,\n                    highlightFill: colorDatasetBase.borderColor,\n                    highlightStroke: colorDatasetBase.borderColor,\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><\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Study of the extent, sources and correlates of variability in drug pharmacokinetics within a patient population.&#8221; Description Certain patient characteristics, such as age, body weight, comorbidity and comedication, can alter the pharmacokinetic parameters of a drug. Population pharmacokinetics seeks to assess the extent of the variability of these parameters among a patient population and to &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/profiles\/population-pharmacokinetics\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Population Pharmacokinetics&#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-152","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/152","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=152"}],"version-history":[{"count":130,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/152\/revisions"}],"predecessor-version":[{"id":1331,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/152\/revisions\/1331"}],"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=152"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}