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<meta name="citation_doi" content="10.1067/mem.2000.107002" />
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<meta property=og:description content="Study Objective: The elimination kinetics of ethylene glycol (EG) in human subjects treated with fomepizole (4-methylpyrazole) were analyzed to establ…" />
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<meta name="citation_title" content="Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management" />
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<title>Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management - ScienceDirect</title>
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href="/science/journal/01960644">Annals of Emergency Medicine</a></h2><div class="text-xs"><a title="Go to table of contents for this volume/issue" href="/science/journal/01960644/36/2">Volume 36, Issue 2</a>, <!-- -->August 2000<!-- -->, Pages 114-125</div></div><div class="publication-cover u-show-from-sm"><a href="/science/journal/01960644/36/2"><img class="publication-cover-image" src="https://ars.els-cdn.com/content/image/1-s2.0-S0196064421X00042-cov150h.gif" alt="Annals of Emergency Medicine" /></a></div></div><h1 id="screen-reader-main-title" class="Head u-font-serif u-h2 u-margin-s-ver"><div class="article-dochead"><span>Toxicology</span></div><span class="title-text">Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management</span><a name="baep-article-footnote-id1" href="#aep-article-footnote-id1" class="workspace-trigger label">*</a>,<a name="baep-article-footnote-id2" href="#aep-article-footnote-id2" class="workspace-trigger label">**</a>,<a name="baep-article-footnote-id3" href="#aep-article-footnote-id3" class="workspace-trigger label">*</a></h1><div class="article-presented"><span class="size-m"><span>Presented in part at the North American Congress of Clinical Toxicology annual meeting, Orlando, FL, September 1998.</span></span></div><div class="Banner" id="banner"><div class="wrapper truncated"><div class="AuthorGroups text-xs"><div class="author-group" id="author-group"><span class="sr-only">Author links open overlay panel</span><a class="author size-m workspace-trigger" name="baep-author-id4" href="#!"><span class="content"><span class="text given-name">Marco L.A.</span><span class="text surname">Sivilotti</span><span class="text degrees">MD, MSc<sup>*‡</sup></span></span></a><a class="author size-m workspace-trigger" name="baep-author-id5" href="#!"><span class="content"><span class="text given-name">Michael J.</span><span class="text surname">Burns</span><span class="text degrees">MD<sup>*‡</sup></span></span></a><a class="author size-m workspace-trigger" name="baep-author-id6" href="#!"><span class="content"><span class="text given-name">Kenneth E.</span><span class="text surname">McMartin</span><span class="text degrees">PhD<sup>§</sup></span></span></a><a class="author size-m workspace-trigger" name="baep-author-id7" href="#!"><span class="content"><span class="text given-name">Jeffrey</span><span class="text surname">Brent</span><span class="text degrees">MD, PhD<sup>∥¶</sup></span></span></a><a class="author size-m workspace-trigger" name="baep-collaboration-id8" href="#!"><span class="content"><span class="text">For the Methylpyrazole for Toxic Alcohols Study Group</span></span></a></div></div></div><button id="show-more-btn" class="button show-hide-details button-primary" type="button" data-aa-button="icon-expand"><span class="button-text">Show more</span><svg focusable="false" viewBox="0 0 92 128" height="20" width="17.25" class="icon 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href="https://urldefense.com/v3/__https://s100.copyright.com/AppDispatchServlet?publisherName=ELS&contentID=S0196064400100976&orderBeanReset=true__;!!GobTDDpD7A!doGuRlsZ67eFC6UNNS3el2mZaP5isqoXcgoeJmjJfchhxd4SWrkdVr--gtVxJrZWFqeLXQ$">Get rights and content</a></div><section class="ReferencedArticles"></section><section class="ReferencedArticles"></section><div class="PageDivider"></div><div class="Abstracts u-font-serif" id="abstracts"><div class="abstract author" id="aep-abstract-id10"><h2 class="section-title u-h3 u-margin-l-top u-margin-xs-bottom">Abstract</h2><div id="aep-abstract-sec-id11"><p id="simple-para.0020"><strong>Study Objective:</strong> The elimination kinetics of ethylene glycol (EG) in human subjects treated with fomepizole (4-methylpyrazole) were analyzed to establish the efficacy of alcohol dehydrogenase (ADH) inhibition and to characterize elimination pathways. <strong>Methods:</strong> Drug concentration data from patients enrolled in the EG arm of the Methylpyrazole for Toxic Alcohols trial, a prospective, multicenter, open-label trial of fomepizole, were analyzed and compared with published estimates. <strong>Results:</strong> In 19 patients analyzed (EG concentrations of 3.5 to 211 mg/dL), elimination was first order during fomepizole monotherapy (half-life of 19.7±1.3 hours) and was not affected by the presence of ethanol. The elimination rate was significantly faster (half-life of <8.6±1.1 hours, <em>P</em> <.001) in the absence of fomepizole and ethanol. EG elimination by the kidneys was directly proportional to remaining renal function as estimated by creatinine clearance, with a fractional excretion of 25.5%±9.4%. Renal elimination and hemodialysis were the only significant routes of EG elimination as long as fomepizole concentrations were maintained well above 10 μmol/L (EG/fomepizole molar ratio, <100:1). All patients with normal serum creatinine concentrations at the initiation of fomepizole treatment had rapid rates of renal elimination (half-life of 16.8±0.8 hours). <strong>Conclusion:</strong> At doses used, fomepizole effectively inhibits ADH-mediated metabolism of EG. Serum creatinine concentration at presentation and creatinine clearance can be used to predict EG elimination during fomepizole therapy and can help determine which patients will require hemodialysis to expedite EG elimination. An absolute EG concentration above 50 mg/dL should no longer be used as an independent criterion for hemodialysis in patients treated with fomepizole. [Sivilotti MLA, Burns MJ, McMartin KE, Brent J, for the Methylpyrazole for Toxic Alcohols Study Group. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. <em>Ann Emerg Med.</em> August 2000;36:114-125.]</p></div></div></div><ul id="issue-navigation" class="issue-navigation u-margin-s-bottom u-bg-grey1"><li class="previous move-left u-padding-s-ver u-padding-s-left"><button class="button-alternative button-alternative-tertiary" disabled="" type="button"><svg focusable="false" viewBox="0 0 54 128" width="32" height="32" class="icon icon-navigate-left"><path d="m1 61l45-45 7 7-38 38 38 38-7 7z"></path></svg><span class="button-alternative-text"><strong>Previous </strong><span class="extra-detail-1">article</span><span class="extra-detail-2"> in issue</span></span></button></li><li class="next move-right u-padding-s-ver u-padding-s-right"><button class="button-alternative button-alternative-tertiary" disabled="" type="button"><span class="button-alternative-text"><strong>Next </strong><span class="extra-detail-1">article</span><span class="extra-detail-2"> in issue</span></span><svg focusable="false" viewBox="0 0 54 128" width="32" height="32" class="icon icon-navigate-right"><path d="m1 99l38-38-38-38 7-7 45 45-45 45z"></path></svg></button></li></ul><div class="related-content-links u-hide-from-md"><button class="button button-anchor" type="button"><span class="button-text">Recommended articles</span></button><button class="button button-anchor" disabled="" type="button"><span class="button-text">Citing articles (0)</span></button></div><div class="Tail"></div><div class="Footnotes"><dl class="footnote"><dt class="footnote-label"><sup><a href="#baep-article-footnote-id1">*</a></sup></dt><dd class="u-margin-xxl-left"><p>Supported by a grant from Orphan Medical Inc, Minnetonka, MN, and by an Orphan Drug Development grant (FDR-001256-01) from the United States Food and Drug Administration. Dr. McMartin receives royalty and consultancy fees from Orphan Medical.</p></dd></dl><dl class="footnote"><dt class="footnote-label"><sup><a href="#baep-article-footnote-id2">**</a></sup></dt><dd class="u-margin-xxl-left"><p><em>Other members of the Methylpyrazole for Toxic Alcohols (META) Study Group are listed in the Appendix.</em></p></dd></dl><dl class="footnote"><dt class="footnote-label"><sup><a href="#baep-article-footnote-id3">*</a></sup></dt><dd class="u-margin-xxl-left"><p>Address for reprints: Marco L. A. Sivilotti, MD, MSc, Department of Emergency Medicine, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada; 613-737-8136, fax 613-737-8470; E-mail <a href="/cdn-cgi/l/email-protection#5a3729332c3336352e2e331a352e2e3b2d3b3235292a332e3b3674353474393b" target="_blank" rel="noreferrer noopener"><span class="__cf_email__" data-cfemail="d1bca2b8a7b8bdbea5a5b891bea5a5b0a6b0b9bea2a1b8a5b0bdffbebfffb2b0">[email protected]</span></a>.</p></dd></dl></div><a class="anchor abstract-link" href="/science/article/abs/pii/S0196064400100976"><span class="anchor-text">View Abstract</span></a><div class="Copyright"><span class="copyright-line">Copyright © 2000 American College of Emergency Physicians. Published by Mosby, Inc. 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<script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script><script type="application/json" data-iso-key="_0">{"abstracts":{"content":[{"$$":[{"$":{"id":"st0010"},"#name":"section-title","_":"Abstract"},{"$$":[{"$$":[{"#name":"bold","_":"Study Objective:"},{"#name":"__text__","_":" The elimination kinetics of ethylene glycol (EG) in human subjects treated with fomepizole (4-methylpyrazole) were analyzed to establish the efficacy of alcohol dehydrogenase (ADH) inhibition and to characterize elimination pathways. "},{"#name":"bold","_":"Methods:"},{"#name":"__text__","_":" Drug concentration data from patients enrolled in the EG arm of the Methylpyrazole for Toxic Alcohols trial, a prospective, multicenter, open-label trial of fomepizole, were analyzed and compared with published estimates. "},{"#name":"bold","_":"Results:"},{"#name":"__text__","_":" In 19 patients analyzed (EG concentrations of 3.5 to 211 mg/dL), elimination was first order during fomepizole monotherapy (half-life of 19.7±1.3 hours) and was not affected by the presence of ethanol. The elimination rate was significantly faster (half-life of <8.6±1.1 hours, "},{"#name":"italic","_":"P"},{"#name":"__text__","_":" <.001) in the absence of fomepizole and ethanol. EG elimination by the kidneys was directly proportional to remaining renal function as estimated by creatinine clearance, with a fractional excretion of 25.5%±9.4%. Renal elimination and hemodialysis were the only significant routes of EG elimination as long as fomepizole concentrations were maintained well above 10 μmol/L (EG/fomepizole molar ratio, <100:1). All patients with normal serum creatinine concentrations at the initiation of fomepizole treatment had rapid rates of renal elimination (half-life of 16.8±0.8 hours). "},{"#name":"bold","_":"Conclusion:"},{"#name":"__text__","_":" At doses used, fomepizole effectively inhibits ADH-mediated metabolism of EG. Serum creatinine concentration at presentation and creatinine clearance can be used to predict EG elimination during fomepizole therapy and can help determine which patients will require hemodialysis to expedite EG elimination. An absolute EG concentration above 50 mg/dL should no longer be used as an independent criterion for hemodialysis in patients treated with fomepizole. [Sivilotti MLA, Burns MJ, McMartin KE, Brent J, for the Methylpyrazole for Toxic Alcohols Study Group. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. "},{"#name":"italic","_":"Ann Emerg Med."},{"#name":"__text__","_":" August 2000;36:114-125.]"}],"$":{"view":"all","id":"simple-para.0020"},"#name":"simple-para"}],"$":{"id":"aep-abstract-sec-id11"},"#name":"abstract-sec"}],"$":{"id":"aep-abstract-id10","class":"author"},"#name":"abstract"}],"floats":[],"footnotes":[],"attachments":[]},"adobeTarget":{},"article":{"analyticsMetadata":{"accountId":"38898","accountName":"State University of New York Upstate Medical University - University Hospital","loginStatus":"anonymous","userId":"36332127","isLoggedIn":false},"cid":"272873","content-family":"serial","copyright-line":"Copyright © 2000 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.","cover-date-years":["2000"],"cover-date-start":"2000-08-01","cover-date-text":"August 2000","document-subtype":"fla","document-type":"article","entitledToken":"88C92711FD97EC8E8AF1C30C5D3464FDC1FA5BF6A2999D3225952529D4ACA16895C8764070D61587","eid":"1-s2.0-S0196064400100976","doi":"10.1067/mem.2000.107002","first-fp":"114","hub-eid":"1-s2.0-S0196064400X0011X","issuePii":"S0196064400X0011X","iss-first":"2","item-weight":"FULL-TEXT","language":"en","last-lp":"125","last-author":{"#name":"last-author","$":{"xmlns:ce":true,"xmlns:dm":true,"xmlns:sb":true},"$$":[{"#name":"author","$":{"id":"aep-author-id7"},"$$":[{"#name":"given-name","_":"Jeffrey"},{"#name":"surname","_":"Brent"},{"#name":"degrees","$$":[{"#name":"__text__","_":"MD, PhD"},{"#name":"sup","$":{"loc":"post"},"_":"∥¶"}]}]}]},"normalized-first-auth-initial":"M","normalized-first-auth-surname":"SIVILOTTI","pages":[{"last-page":"125","first-page":"114"}],"pii":"S0196064400100976","srctitle":"Annals of Emergency Medicine","timestamp":"2015-05-14T05:44:01.949088-04:00","title":{"content":[{"#name":"article-footnote","$":{"id":"aep-article-footnote-id1"},"$$":[{"#name":"label","_":"*"},{"#name":"note-para","_":"Supported by a grant from Orphan Medical Inc, Minnetonka, MN, and by an Orphan Drug Development grant (FDR-001256-01) from the United States Food and Drug Administration. Dr. McMartin receives royalty and consultancy fees from Orphan Medical."}]},{"#name":"article-footnote","$":{"id":"aep-article-footnote-id2"},"$$":[{"#name":"label","_":"**"},{"#name":"note-para","$$":[{"#name":"italic","_":"Other members of the Methylpyrazole for Toxic Alcohols (META) Study Group are listed in the Appendix."}]}]},{"#name":"article-footnote","$":{"id":"aep-article-footnote-id3"},"$$":[{"#name":"label","_":"*"},{"#name":"note-para","$$":[{"#name":"__text__","_":"Address for reprints: Marco L. A. Sivilotti, MD, MSc, Department of Emergency Medicine, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada; 613-737-8136, fax 613-737-8470; E-mail "},{"#name":"inter-ref","$":{"xmlns:xlink":true,"href":"mailto:msivilotti@ottawahospital.on.ca","type":"simple"},"_":"msivilotti@ottawahospital.on.ca"},{"#name":"__text__","_":"."}]}]},{"#name":"dochead","$$":[{"#name":"textfn","_":"Toxicology"}]},{"#name":"title","_":"Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management"}],"floats":[],"footnotes":[{"#name":"article-footnote","$":{"id":"aep-article-footnote-id1"},"$$":[{"#name":"label","_":"*"},{"#name":"note-para","_":"Supported by a grant from Orphan Medical Inc, Minnetonka, MN, and by an Orphan Drug Development grant (FDR-001256-01) from the United States Food and Drug Administration. 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