{"id":131,"date":"2019-04-24T12:45:33","date_gmt":"2019-04-24T12:45:33","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=131"},"modified":"2020-09-04T03:30:33","modified_gmt":"2020-09-04T03:30:33","slug":"elimination-kinetics","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/elimination-kinetics\/","title":{"rendered":"Elimination Kinetics"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">Zero-order elimination kinetics  :&nbsp;&#8220;Elimination of a constant quantity per time unit of the drug quantity  present in the organism.&#8221;  <\/h2>\n\n\n\n<h2 class=\"wp-block-heading\">First order elimination kinetics  :&nbsp;&#8220;Elimination of a constant fraction per time unit of the drug quantity  present in the organism. The elimination is proportional to the drug  concentration.&#8221; <\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p><strong>Zero-order elimination kinetics :<\/strong>\n<\/p>\n\n\n\n<p>The plasma concentration \u2013 time profile during the elimination phase is linear (<strong>Fig. 1<\/strong>). For example 1.2 mg are eliminated every hour, independently of the drug concentration in the body.\n<\/p>\n\n\n\n<p>Order 0 elimination is rather rare, mostly occurring\n when the elimination system is saturated. An example is the elimination\n of Ethanol.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter\"><img loading=\"lazy\" decoding=\"async\" width=\"314\" height=\"268\" src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/06\/elimination_zero.gif\" alt=\"\" class=\"wp-image-386\"\/><figcaption> Fig. 1. Zero-order kinetics <\/figcaption><\/figure><\/div>\n\n\n\n<p><strong>First-order elimination kinetics :<\/strong>\n<\/p>\n\n\n\n<p>For first order elimination, the plasma \nconcentration \u2013 time profile during the elimination phase shows an \nexponential decrease in the plot with linear axes (<strong>Fig. 2.<\/strong>) and is linear if plotted on a semi-logarithmic plot (plasma concentration on logarithmic axis and time on linear axis; <strong>Fig. 3.<\/strong>). \n<\/p>\n\n\n\n<p>For example, 1% of the drug quantity is eliminated per minute. Many drugs are eliminated by first order kinetics. <\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter\"><img loading=\"lazy\" decoding=\"async\" width=\"285\" height=\"240\" src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/06\/elimination_first_lin_01.gif\" alt=\"\" class=\"wp-image-387\"\/><figcaption> Fig. 2. First-order kinetics (linear y-axis) <\/figcaption><\/figure><\/div>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter\"><img loading=\"lazy\" decoding=\"async\" width=\"286\" height=\"240\" src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/06\/elimination_first_log.gif\" alt=\"\" class=\"wp-image-389\"\/><figcaption> Fig. 3. First-order kinetics (log y-axis) <\/figcaption><\/figure><\/div>\n\n\n\n<p>The time course of the decrease of the drug concentration in the plasma can be described by an exponential equation of the form:\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> $$C = C(0)*e^{-\\lambda*\\tau}$$<p class=\"formula\"><\/div>\n\n\n\n<p>with\n<\/p>\n\n\n\n<p><strong>C<\/strong> = drug concentration  <\/p>\n\n\n\n<p><strong>C(0)<\/strong> = extrapolated initial drug concentration (see <a href=\"\/pharmacology\/volumeofdistribution\">Volume of distribution<\/a>) <\/p>\n\n\n\n<p> <strong>\u03bb<\/strong>  = elimination rate constant (see <a href=\"\/pharmacology\/halflife\">Half-life<\/a>) <\/p>\n\n\n\n<p><strong>t<\/strong> = time <\/p>\n\n\n\n<p>The elimination rate constant ? can be calculated by  fitting the data points during the elimination phase to a single  exponential; yielding in this example a ? of 0.34 h<sup>-1<\/sup>. An alternative method (see <strong>Fig. 3.<\/strong>)  consists in plotting the logarithm of the drug plasma concentration as a  function of time, which will yield a straight line. The steepness of  this line equals \u2013?.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical Implications<\/h3>\n\n\n\n<p>In clinical pharmacology, first order kinetics \nare considered as a \u00ab linear process \u00bb, because the rate of elimination \nis proportional to the drug concentration. This means that the higher \nthe drug concentration, the higher its elimination rate. In other words,\n the elimination processes are not saturated and can adapt to the needs \nof the body, to reduce accumulation of the drug.\n<\/p>\n\n\n\n<p>95% of the drugs in use at therapeutic concentrations are eliminated by first order elimination kinetics.\n<\/p>\n\n\n\n<p>A few substances are eliminated by zero-order \nelimination kinetics, because their elimination process is saturated. \nExamples are Ethanol, Phenytoin, Salicylates, Cisplatin, Fluoxetin, \nOmeprazol. \n<\/p>\n\n\n\n<p>Because in a saturated process the elimination rate  is no longer proportional to the drug concentration but decreasing at  higher concentrations, zero-order kinetics are also called \u201c<a href=\"\/pharmacology\/non-linear-kinetics\">non-linear kinetics<\/a>\u201d in clinical pharmacology. <\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Terminology and properties<\/h4>\n\n\n\n<table class=\"wp-block-table\"><tbody><tr><td> <strong>Elimination kinetics<\/strong> <\/td><td> <strong>First order<\/strong><\/td><td> <strong>Zero order<\/strong> <\/td><\/tr><tr><td> <strong>Curve in the plasma concentration vs. time plot after i.v. bolus<\/strong> <\/td><td> Exponential decay (Fig. 2) <\/td><td>Linear (Fig. 1)  <\/td><\/tr><tr><td> <strong>Curve in the log plasma concentration vs. time plot after i.v. bolus<\/strong> <\/td><td>Linear (Fig. 3) <\/td><td>Non-linear <\/td><\/tr><tr><td> <strong>Relation between elimination rate and drug concentration<\/strong> <\/td><td>Elimination rate is proportional to drug concentration <\/td><td>Elimination rate saturates with higher drug concentration&lt; <\/td><\/tr><tr><td> <strong>Term in clinical pharmacology<\/strong> <\/td><td>Linear kinetics <\/td><td>Non linear kinetics <\/td><\/tr><tr><td> <strong>Concerns<\/strong> <\/td><td>95 % of drugs, at therapeutic concentrations  <\/td><td>The remaining 5 %, and ethanol<\/td><\/tr><\/tbody><\/table>\n","protected":false},"excerpt":{"rendered":"<p>Zero-order elimination kinetics :&nbsp;&#8220;Elimination of a constant quantity per time unit of the drug quantity present in the organism.&#8221; First order elimination kinetics :&nbsp;&#8220;Elimination of a constant fraction per time unit of the drug quantity present in the organism. The elimination is proportional to the drug concentration.&#8221; Description Zero-order elimination kinetics : The plasma concentration &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/elimination-kinetics\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Elimination Kinetics&#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-131","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/131","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=131"}],"version-history":[{"count":28,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/131\/revisions"}],"predecessor-version":[{"id":1310,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/131\/revisions\/1310"}],"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=131"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}