107 lines
42 KiB
Text
107 lines
42 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK548701">
|
|
<meta name="ncbi_domain" content="livertox">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK548701/?report=reader">
|
|
<meta name="ncbi_pagename" content="Cysteamine - LiverTox - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Cysteamine - LiverTox - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="jr-prev-unit" content="/books/n/livertox/Cyproterone/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/livertox/IvacaftorLumacaftor/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/livertox/?report=toc">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]">
|
|
<meta name="citation_title" content="Cysteamine">
|
|
<meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="citation_date" content="2017/11/03">
|
|
<meta name="citation_pmid" content="31644011">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK548701/">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Cysteamine">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
|
|
<meta name="DC.Date" content="2017/11/03">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK548701/">
|
|
<meta name="description" content="Cysteamine is a simple aminothiol molecule that is used to treat nephropathic cystinosis, due to its ability to decrease the markedly elevated and toxic levels of intracellular cystine that occur in this disease and cause its major complications. Cysteamine has been associated with serum enzyme elevations when given intravenously in high doses, but it has not been shown to cause clinically apparent acute liver injury.">
|
|
<meta name="og:title" content="Cysteamine">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="Cysteamine is a simple aminothiol molecule that is used to treat nephropathic cystinosis, due to its ability to decrease the markedly elevated and toxic levels of intracellular cystine that occur in this disease and cause its major complications. Cysteamine has been associated with serum enzyme elevations when given intravenously in high doses, but it has not been shown to cause clinically apparent acute liver injury.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK548701/">
|
|
<meta name="og:site_name" content="NCBI Bookshelf">
|
|
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-livertox-lrg.png">
|
|
<meta name="twitter:card" content="summary">
|
|
<meta name="twitter:site" content="@ncbibooks">
|
|
<meta name="bk-non-canon-loc" content="/books/n/livertox/Cysteamine/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK548701/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8DB71D7D7C27A10000000000B00095.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK548701/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/livertox/Cyproterone/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">Cysteamine</div><div class="j">LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]</div></div><div class="tail"><a href="/books/n/livertox/IvacaftorLumacaftor/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK548701/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK548701/&text=Cysteamine"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/livertox/?report=reader">Title Information</a><a href="/books/n/livertox/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK548701/?report=classic">Switch to classic view</a><a href="/books/NBK548701/pdf/Bookshelf_NBK548701.pdf">PDF (111K)</a><a href="/books/NBK548701/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK548701%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8DB71D7D7C27A10000000000B00095.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK548701_"><span class="title" itemprop="name">Cysteamine</span></h1><p class="fm-aai"><a href="#_NBK548701_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Cysteamine.OVERVIEW"><h2 id="_Cysteamine_OVERVIEW_">OVERVIEW</h2><div id="Cysteamine.Introduction"><h3>Introduction</h3><p>Cysteamine is a simple aminothiol molecule that is used to treat nephropathic cystinosis, due to its ability to decrease the markedly elevated and toxic levels of intracellular cystine that occur in this disease and cause its major complications. Cysteamine has been associated with serum enzyme elevations when given intravenously in high doses, but it has not been shown to cause clinically apparent acute liver injury.</p></div><div id="Cysteamine.Background"><h3>Background</h3><p>Cysteamine (sis tee' a meen) is a simple aminothiol molecule which is used to treat nephropathic cystinosis, a rare autosomal recessive disorder characterized by progressive renal tubular dysfunction and growth retardation, and which eventually leads to renal failure and need for dialysis or renal transplantation often within the first decade of life. The underlying defect in cystinosis is a deficiency of an amino acid carrier that transports cystine out of lysosomes. The absence of this transporter causes accumulation of toxic levels of cystine in tissues. Those organs most susceptible to the toxic effects of cystine include the kidney, endocrine tissue, eyes and muscle. Cysteamine readily penetrates cells and is concentrated in lysosomes where it acts by converting intralysosomal cystine to cysteine which is readily transported out of lysosomes. This action leads to a decrease in cellular cystine levels and prevents the renal failure, growth retardation and many of the other chronic complications of nephropathic cystinosis. Cysteamine was approved for the therapy of cystinosis in the United States in 1994. It is now available in several forms including cysteamine bitartrate salt under the commercial name Cystagon (given every 6 hours), as well as a delayed release preparation under the name ProCysBi (given every 12 hours). The typical maintenance dose is 2.0 grams daily in adults and children above the age of 12, and 1.3 to 1.95 grams/m<sup>2</sup> daily in younger children. Cysteamine is usually initiated using a fraction of the maintenance dose, with gradual dose escalation. Both preparations of cysteamine have an unpleasant taste and odor which makes compliance with taking the high doses required to control intracellular cystine levels in cystinosis a frequent problem. Common side effects include nausea, anorexia, fatigue and diarrhea. Rare, but potentially severe adverse reactions include rash, skin fragility and benign intracranial hypertension. Joint hyperextension, leg pains, osteopenia, fractures and scoliosis also occur in cysteamine treated patients with cystinosis, but are more likely complications of the underlying disease than adverse effects due to cysteamine.</p></div><div id="Cysteamine.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>During long term use of cysteamine in preregistration studies, serum ALT elevations occurred in a small proportion of treated subjects, but the background rate of serum enzyme elevations in this population is high and was not defined in the open label studies. There have been reports of more marked enzyme elevations during high dose therapy with cysteamine, with recurrence on reexposure. These abnormalities were invariably asymptomatic and rapidly reversed with dose adjustment. In addition, patients with cystinosis appear to be at risk for developing nodular regenerative hyperplasia and noncirrhotic portal hypertension. The role of long term cysteamine therapy in these hepatic complications is not clear. There have been no reports of clinically apparent, acute liver injury with jaundice attributable to cysteamine, although it has had only limited wide scale use.</p><p>Likelihood score: D[HD] (possible cause of liver injury when given in high doses).</p></div><div id="Cysteamine.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>The mechanism by which cysteamine might lead to serum enzyme elevations or liver injury is not known. Cysteamine is metabolized in most cells and it does not seem to be a substrate for or affect the hepatic cytochrome P450 system. In clinical trials of cysteamine, no evidence of drug-drug interactions was identified.</p></div><div id="Cysteamine.Outcome_and_Management"><h3>Outcome and Management</h3><p>Serum enzyme elevations during cysteamine therapy are generally mild and self-limited, resolving even without drug interruption or dose reduction. Other causes of liver injury should be sought before assuming that the abnormalities are due to cysteamine.</p><p>Drug Class: Genetic Disorder Agents</p></div></div><div id="Cysteamine.PRODUCT_INFORMATION"><h2 id="_Cysteamine_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Cysteamine.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Cysteamine Bitartrate – Cystagon®</p><p>Cysteamine Bitartrate (Delayed Release) – ProCysBi®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Genetic Disorder Agents</p><p>
|
|
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Cysteamine" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
|
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></div><div id="Cysteamine.CHEMICAL_FORMULA_AND_STRUCTUR"><h2 id="_Cysteamine_CHEMICAL_FORMULA_AND_STRUCTUR_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCysteamineT1"><a href="/books/NBK548701/table/Cysteamine.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figCysteamineT1" rid-ob="figobCysteamineT1"><img class="small-thumb" src="/books/NBK548701/table/Cysteamine.T1/?report=thumb" src-large="/books/NBK548701/table/Cysteamine.T1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="Cysteamine.T1"><a href="/books/NBK548701/table/Cysteamine.T1/?report=objectonly" target="object" rid-ob="figobCysteamineT1">Table</a></h4></div></div></div><div id="Cysteamine.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Cysteamine_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 03 November 2017</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Cysteamine.R1">Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999: pp. 731-4.<div><i>(Expert review of hepatotoxicity published in 1999; cysteamine is not discussed).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R2">Gahl WA, Bashan N, Tietze F, Bernardini I, Schulman JD. Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science 1982; 217 (4566): 1263-5. [<a href="https://pubmed.ncbi.nlm.nih.gov/7112129" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7112129</span></a>]<div><i>(Demonstration of defective transporter for cystine in lysosomes from patients with cystinosis which results in a toxic accumulation of cystine; in contrast, the egress of methionine, tryptophan and other amino acids is normal, suggesting a specific amino acid transporter defect).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R3">Avner ED, Ellis D, Jaffee R. Veno-occlusive disease of the liver associated with cysteamine treatment of nephropathic cystinosis. J Pediatr 1983; 102: 793-6. [<a href="https://pubmed.ncbi.nlm.nih.gov/6842343" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6842343</span></a>]<div><i>(8 year old boy with nephropathic cystinosis developed ascites and gastrointestinal bleeding from gastric varices 22 months after starting cysteamine [bilirubin not given, ALT 16 U/L, Alk P 68 U/L, protime 19 sec], biopsy showing changes of sinusoidal obstruction syndrome).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R4">Gahl WA, Schulman JD, Thoene JG, Schneider J. Hepatotoxicity of cysteamine? J Pediatr 1983; 103: 1008-9. [<a href="https://pubmed.ncbi.nlm.nih.gov/6644413" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6644413</span></a>]<div><i>(Letter in response to Avner [1983] suggesting that sinusoidal obstruction syndrome may be a part of the clinical spectrum of cystinosis, rather than a complication of cysteamine therapy).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R5">Gahl WA, Schneider JA, Thoene JG, Chesney R. Course of nephropathic cystinosis after age 10 years. J Pediatr 1986; 109: 605-8. [<a href="https://pubmed.ncbi.nlm.nih.gov/3531450" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3531450</span></a>]<div><i>(Among 80 patients with nephropathic cystinosis above the age of 10 identified in a US wide survey, 90% had undergone renal transplant [at an average age of 10 years] and the oldest child without transplant was 14 and on dialysis; other complications included hepatomegaly [42%] and splenomegaly, but liver tests were abnormal in only 11 [14%] who had mild ALT or AST elevations; other late complications included photophobia, decreased visual acuity and hypothyroidism).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R6">Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, Denman DW, et al. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 1987; 316: 971-7. [<a href="https://pubmed.ncbi.nlm.nih.gov/3550461" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3550461</span></a>]<div><i>(Among 93 children with nephropathic cystinosis treated with cysteamine hydrochloride [mean dose 51 mg/kg daily] for up to 6 years, leucocyte cystine concentrations decreased by 82%, renal function stabilized and growth was improved in comparison to historical controls who were not treated; side effects included nausea [from its taste and odor] and one child developed sinusoidal obstruction syndrome which was attributed to the underlying disease, rather than cysteamine).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R7">Gahl WA, Thoene JG, Schneider JA, O'Regan S, Kaiser-Kupfer MI, Kuwabara T. NIH conference. Cystinosis: progress in a prototypic disease. Ann Intern Med 1988; 109: 557-69. [<a href="https://pubmed.ncbi.nlm.nih.gov/3048161" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3048161</span></a>]<div><i>(Review of the clinical characteristics, epidemiology, pathogenesis, complications and therapy of cystinosis).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R8">Kimonis VE, Troendle JR, Rose SR, Yang ML, Markello TC, Gahl WA. Effects of early cysteamine therapy on thyroid function and growth in nephropathic cystinosis. J Clin Endocrinol Metab 1995; 80: 3257-61. [<a href="https://pubmed.ncbi.nlm.nih.gov/7593434" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7593434</span></a>]<div><i>(Among 101 patients with nephropathic cystinosis treated with cysteamine, those started on therapy before the age of 2 and who maintained optimal leukocyte cystine levels [n=24] had lower rates of hypothyroidism and better growth and bone age than those with partial [n=36] or poor or delayed [n=47] treatment responses).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R9">Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002; 347: 111-21. [<a href="https://pubmed.ncbi.nlm.nih.gov/12110740" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12110740</span></a>]<div><i>(Review of the history, clinical characteristics, clinical variants, complications, genetics, diagnosis and treatment of cystinosis).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R10">Kleta R, Gahl WA. Pharmacological treatment of nephropathic cystinosis with cysteamine. Expert Opin Pharmacother 2004; 5: 2255-62. [<a href="https://pubmed.ncbi.nlm.nih.gov/15500372" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15500372</span></a>]<div><i>(Review of cysteamine therapy of cystinosis; states that early diagnosis and therapy with cysteamine can guarantee normal growth and maintenance of renal function).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R11">Kleta R, Bernardini I, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, Gahl WA. Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr 2004; 145: 555-60. [<a href="https://pubmed.ncbi.nlm.nih.gov/15480385" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15480385</span></a>]<div><i>(Long term course of two siblings with cystinosis who were started on cysteamine therapy at 2 and 20 months of age, and both achieved normal growth and maintained normal renal function [creatinine clearance of 78 and 105 mL/min] for 8 and 12 years).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R12">Kleta R, Kaskel F, Dohil R, Goodyer P, Guay-Woodford LM, Harms E, Ingelfinger JR, et al.; NIH Office of Rare Diseases. First NIH/Office of Rare Diseases Conference on Cystinosis: past, present, and future. Pediatr Nephrol 2005; 20: 452-4. [<a href="https://pubmed.ncbi.nlm.nih.gov/15747161" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15747161</span></a>]<div><i>(Brief summary of the major clinical challenges in cystinosis including early diagnosis, improved therapeutics, better compliance and transition of care from pediatric to adult medical services).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R13">O'Brien K, Hussain N, Warady BA, Kleiner DE, Kleta R, Bernardini I, Heller T, et al. Nodular regenerative hyperplasia and severe portal hypertension in cystinosis. Clin Gastroenterol Hepatol 2006; 4: 387-94. [<a href="https://pubmed.ncbi.nlm.nih.gov/16527704" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16527704</span></a>]<div><i>(Two adults, ages 19 and 30 years, with nephropathic cystinosis but minimal exposure to cysteamine were found to have severe noncirrhotic portal hypertension, and liver biopsies demonstrated nodular regenerative hyperplasia with minimal portal fibrosis, the etiology of which was unknown).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R14">Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med 2007; 147: 242-50. [<a href="https://pubmed.ncbi.nlm.nih.gov/17709758" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17709758</span></a>]<div><i>(Among 100 adults with nephropathic cystinosis, 92 had a kidney transplants and at least half had hypothyroidism, hypergonadism, pulmonary insufficiency, swallowing disorders and myopathy, one-third had retinopathy and one quarter diabetes; cysteamine therapy was associated with delay in need for renal allograft and fewer complications and deaths).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R15">Bendel-Stenzel MR, Steinke J, Dohil R, Kim Y. Intravenous delivery of cysteamine for the treatment of cystinosis: association with hepatotoxicity. Pediatr Nephrol 2008; 23: 311-5. [<a href="https://pubmed.ncbi.nlm.nih.gov/17668247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17668247</span></a>]<div><i>(Two year old girl with severe nephropathic cystinosis and intolerance to oral cysteamine was treated with an intravenous form [5-6 mg/kg every 8 hours] which resulted in decreases in intracellular cystine, but was followed after 50 days by marked elevations in serum ALT [2117 U/L] and AST [1362 U/L] without jaundice [bilirubin 0.4 mg/dL], levels promptly falling on stopping the infusions and recurring with intravenous rechallenge [ALT ~140 U/L after 25 days], and later with oral rechallenge using cysteamine bitartrate [ALT 249 U/L after 6 months]).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R16">Besouw MT, Bowker R, Dutertre JP, Emma F, Gahl WA, Greco M, Lilien MR, et al. Cysteamine toxicity in patients with cystinosis. J Pediatr 2011; 159: 1004-11. [<a href="https://pubmed.ncbi.nlm.nih.gov/21784456" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21784456</span></a>]<div><i>(Among 550 European patients with cystinosis who were treated with cysteamine, 8 developed possible toxicity, 6 of whom developed vascular lesions over the elbow marked by irregular collagen fibers and angioendotheliomatosis, other complications were leg pains and neurologic symptoms which improved with lowering the dose; possibly due to inhibition of cross linking of collagen).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R17">Dohil R, Schmeltzer S, Cabrera BL, Wang T, Durelle J, Duke KB, Schwimmer JB, et al. Enteric-coated cysteamine for the treatment of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2011; 33: 1036-44. [<a href="https://pubmed.ncbi.nlm.nih.gov/21395631" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21395631</span></a>]<div><i>(Among 11 children [>10 years] with nonalcoholic fatty liver disease and raised serum ALT levels treated with enteric coated cysteamine [15 mg/kg daily], mean ALT levels fell [from 120 to 55 U/L], with no change in weight and rise of ALT values after stopping therapy [to 74 U/L).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R18">Langman CB, Greenbaum LA, Sarwal M, Grimm P, Niaudet P, Deschênes G, Cornelissen E, et al. A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety. Clin J Am Soc Nephrol 2012; 7: 1112-20. [<a href="/pmc/articles/PMC3386675/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3386675</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22554716" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22554716</span></a>]<div><i>(Among 43 patients with cystinosis treated with standard cysteamine [every 6 hours] or a new formulation of enteric coated, delayed release form of cysteamine bitartrate [every 12 hours] for 3 weeks with subsequent cross over, mean peak white cell cystine levels were similar, but gastrointestinal side effects were greater with the delayed release form).</i></div></div></li><li><div class="bk_ref" id="Cysteamine.R19">Schwimmer JB, Lavine JE, Wilson LA, Neuschwander-Tetri BA, Xanthakos SA, Kohil R, Barlow S, et al. In children with nonalcoholic fatty liver disease, cysteamine bitartrate delayed-release improves liver enzymes but does not reduce disease activity scores. Gastroenterol 2016: 151: 1141-54. [<a href="/pmc/articles/PMC5124386/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5124386</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27569726" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27569726</span></a>]<div><i>(Among 169 children with nonalcoholic fatty liver treated with cysteamine [150 to 450 mg daily] or placebo for 48 weeks, ALT and AST levels improved significantly, but histologic changes were minimal; no patient developed clinically worsening or clinically apparent liver injury).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548701_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">November 3, 2017</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Cysteamine. [Updated 2017 Nov 3].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Cyproterone/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/IvacaftorLumacaftor/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="boxed-text" id="figobCysteamineBPI"><div id="Cysteamine.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
|
|
<b>REPRESENTATIVE TRADE NAMES</b>
|
|
</p><p>Cysteamine Bitartrate – Cystagon®</p><p>Cysteamine Bitartrate (Delayed Release) – ProCysBi®</p><p>
|
|
<b>DRUG CLASS</b>
|
|
</p><p>Genetic Disorder Agents</p><p>
|
|
<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Cysteamine" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
|
|
</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></article><article data-type="table-wrap" id="figobCysteamineT1"><div id="Cysteamine.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548701/table/Cysteamine.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Cysteamine.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Cysteamine.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Cysteamine.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NO.</th><th id="hd_h_Cysteamine.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Cysteamine.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Cysteamine.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Cysteamine</td><td headers="hd_h_Cysteamine.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135117680" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">27761-19-9</a>
|
|
</td><td headers="hd_h_Cysteamine.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">C4-H6-O6.C2-H7-N-S</td><td headers="hd_h_Cysteamine.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK548701/bin/Cysteamine_structure.jpg" alt="Cysteamine Chemical Structure" /></div>
|
|
</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal106 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|