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class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-cs mw-list-item"><a href="https://cs.wikipedia.org/wiki/Efekt_prvn%C3%ADho_pr%C5%AFchodu" title="Efekt prvního průchodu – Czech" lang="cs" hreflang="cs" data-title="Efekt prvního průchodu" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target"><span>Čeština</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/First-Pass-Effekt" title="First-Pass-Effekt – German" lang="de" hreflang="de" data-title="First-Pass-Effekt" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-et mw-list-item"><a href="https://et.wikipedia.org/wiki/Esmane_maksapassaa%C5%BE" title="Esmane maksapassaaž – Estonian" lang="et" hreflang="et" data-title="Esmane maksapassaaž" data-language-autonym="Eesti" data-language-local-name="Estonian" class="interlanguage-link-target"><span>Eesti</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Efecto_de_primer_paso" title="Efecto de primer paso – Spanish" lang="es" hreflang="es" data-title="Efecto de primer paso" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%A7%D8%AB%D8%B1_%D8%B9%D8%A8%D9%88%D8%B1_%D8%A7%D9%88%D9%84" title="اثر عبور اول – Persian" lang="fa" hreflang="fa" data-title="اثر عبور اول" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Effet_de_premier_passage" title="Effet de premier passage – French" lang="fr" hreflang="fr" data-title="Effet de premier passage" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%EC%B4%88%ED%9A%8C_%ED%86%B5%EA%B3%BC_%ED%9A%A8%EA%B3%BC" title="초회 통과 효과 – Korean" lang="ko" hreflang="ko" data-title="초회 통과 효과" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Effetto_di_primo_passaggio" title="Effetto di primo passaggio – Italian" lang="it" hreflang="it" data-title="Effetto di primo passaggio" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-ku mw-list-item"><a href="https://ku.wikipedia.org/wiki/Tes%C3%AEra_bor%C3%AEna_yek%C3%AA" title="Tesîra borîna yekê – Kurdish" lang="ku" hreflang="ku" data-title="Tesîra borîna yekê" data-language-autonym="Kurdî" data-language-local-name="Kurdish" class="interlanguage-link-target"><span>Kurdî</span></a></li><li class="interlanguage-link interwiki-la mw-list-item"><a href="https://la.wikipedia.org/wiki/Effectus_primi_transitus_(biochemia)" title="Effectus primi transitus (biochemia) – Latin" lang="la" hreflang="la" data-title="Effectus primi transitus (biochemia)" data-language-autonym="Latina" data-language-local-name="Latin" class="interlanguage-link-target"><span>Latina</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/First-pass-effect" title="First-pass-effect – Dutch" lang="nl" hreflang="nl" data-title="First-pass-effect" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E5%88%9D%E5%9B%9E%E9%80%9A%E9%81%8E%E5%8A%B9%E6%9E%9C" title="初回通過効果 – Japanese" lang="ja" hreflang="ja" data-title="初回通過効果" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Efekt_pierwszego_przej%C5%9Bcia" title="Efekt pierwszego przejścia – Polish" lang="pl" hreflang="pl" data-title="Efekt pierwszego przejścia" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Metabolismo_de_primeira_passagem" title="Metabolismo de primeira passagem – Portuguese" lang="pt" hreflang="pt" data-title="Metabolismo de primeira passagem" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ro mw-list-item"><a href="https://ro.wikipedia.org/wiki/Efect_de_prim_pasaj" title="Efect de prim pasaj – Romanian" lang="ro" hreflang="ro" data-title="Efect de prim pasaj" data-language-autonym="Română" data-language-local-name="Romanian" class="interlanguage-link-target"><span>Română</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%AD%D1%84%D1%84%D0%B5%D0%BA%D1%82_%D0%BF%D0%B5%D1%80%D0%B2%D0%BE%D0%B3%D0%BE_%D0%BF%D1%80%D0%BE%D1%85%D0%BE%D0%B6%D0%B4%D0%B5%D0%BD%D0%B8%D1%8F" title="Эффект первого прохождения – Russian" lang="ru" hreflang="ru" data-title="Эффект первого прохождения" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-sl mw-list-item"><a href="https://sl.wikipedia.org/wiki/U%C4%8Dinek_prvega_prehoda" title="Učinek prvega prehoda – Slovenian" lang="sl" hreflang="sl" data-title="Učinek prvega prehoda" data-language-autonym="Slovenščina" data-language-local-name="Slovenian" class="interlanguage-link-target"><span>Slovenščina</span></a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/%D0%9C%D0%B5%D1%82%D0%B0%D0%B1%D0%BE%D0%BB%D0%B8%D0%B7%D0%B0%D0%BC_%D0%BF%D1%80%D0%B2%D0%BE%D0%B3_%D0%BF%D1%80%D0%BE%D0%BB%D0%B0%D0%B7%D0%B0" title="Метаболизам првог пролаза – Serbian" lang="sr" hreflang="sr" data-title="Метаболизам првог пролаза" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target"><span>Српски / srpski</span></a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Metabolizam_prvog_prolaza" title="Metabolizam prvog prolaza – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Metabolizam prvog prolaza" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target"><span>Srpskohrvatski / српскохрватски</span></a></li><li class="interlanguage-link interwiki-fi mw-list-item"><a href="https://fi.wikipedia.org/wiki/Ensikierron_metabolia" title="Ensikierron metabolia – Finnish" lang="fi" hreflang="fi" data-title="Ensikierron metabolia" data-language-autonym="Suomi" data-language-local-name="Finnish" class="interlanguage-link-target"><span>Suomi</span></a></li><li class="interlanguage-link interwiki-sv mw-list-item"><a href="https://sv.wikipedia.org/wiki/F%C3%B6rstapassagemetabolism" title="Förstapassagemetabolism – Swedish" lang="sv" hreflang="sv" data-title="Förstapassagemetabolism" data-language-autonym="Svenska" 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data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">Not to be confused with <a href="/wiki/First_dose_effect" class="mw-redirect" title="First dose effect">First dose effect</a>.</div> <style data-mw-deduplicate="TemplateStyles:r1251242444">.mw-parser-output .ambox{border:1px solid #a2a9b1;border-left:10px solid #36c;background-color:#fbfbfb;box-sizing:border-box}.mw-parser-output .ambox+link+.ambox,.mw-parser-output .ambox+link+style+.ambox,.mw-parser-output .ambox+link+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+style+.ambox,.mw-parser-output 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.mbox-image-div{width:52px}@media(min-width:720px){.mw-parser-output .ambox{margin:0 10%}}@media print{body.ns-0 .mw-parser-output .ambox{display:none!important}}</style><table class="box-More_citations_needed plainlinks metadata ambox ambox-content ambox-Refimprove" role="presentation"><tbody><tr><td class="mbox-image"><div class="mbox-image-div"><span typeof="mw:File"><a href="/wiki/File:Question_book-new.svg" class="mw-file-description"><img alt="" src="//upload.wikimedia.org/wikipedia/en/thumb/9/99/Question_book-new.svg/50px-Question_book-new.svg.png" decoding="async" width="50" height="39" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/9/99/Question_book-new.svg/75px-Question_book-new.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/9/99/Question_book-new.svg/100px-Question_book-new.svg.png 2x" data-file-width="512" data-file-height="399" /></a></span></div></td><td class="mbox-text"><div class="mbox-text-span">This article <b>needs additional citations for <a href="/wiki/Wikipedia:Verifiability" title="Wikipedia:Verifiability">verification</a></b>.<span class="hide-when-compact"> Please help <a href="/wiki/Special:EditPage/First_pass_effect" title="Special:EditPage/First pass effect">improve this article</a> by <a href="/wiki/Help:Referencing_for_beginners" title="Help:Referencing for beginners">adding citations to reliable sources</a>. Unsourced material may be challenged and removed.<br /><small><span class="plainlinks"><i>Find sources:</i> <a rel="nofollow" class="external text" href="https://www.google.com/search?as_eq=wikipedia&q=%22First+pass+effect%22">"First pass effect"</a> – <a rel="nofollow" class="external text" href="https://www.google.com/search?tbm=nws&q=%22First+pass+effect%22+-wikipedia&tbs=ar:1">news</a> <b>·</b> <a rel="nofollow" class="external text" href="https://www.google.com/search?&q=%22First+pass+effect%22&tbs=bkt:s&tbm=bks">newspapers</a> <b>·</b> <a rel="nofollow" class="external text" href="https://www.google.com/search?tbs=bks:1&q=%22First+pass+effect%22+-wikipedia">books</a> <b>·</b> <a rel="nofollow" class="external text" href="https://scholar.google.com/scholar?q=%22First+pass+effect%22">scholar</a> <b>·</b> <a rel="nofollow" class="external text" href="https://www.jstor.org/action/doBasicSearch?Query=%22First+pass+effect%22&acc=on&wc=on">JSTOR</a></span></small></span> <span class="date-container"><i>(<span class="date">December 2016</span>)</i></span><span class="hide-when-compact"><i> (<small><a href="/wiki/Help:Maintenance_template_removal" title="Help:Maintenance template removal">Learn how and when to remove this message</a></small>)</i></span></div></td></tr></tbody></table> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:2138_Hepatic_Portal_Vein_System.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/cf/2138_Hepatic_Portal_Vein_System.jpg/220px-2138_Hepatic_Portal_Vein_System.jpg" decoding="async" width="220" height="142" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/cf/2138_Hepatic_Portal_Vein_System.jpg/330px-2138_Hepatic_Portal_Vein_System.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/cf/2138_Hepatic_Portal_Vein_System.jpg/440px-2138_Hepatic_Portal_Vein_System.jpg 2x" data-file-width="1583" data-file-height="1021" /></a><figcaption>Illustration showing the hepatic portal vein system</figcaption></figure> <p>The <b>first pass effect</b> (also known as <b>first-pass metabolism</b> or <b>presystemic metabolism</b>) is a phenomenon of <a href="/wiki/Drug_metabolism" title="Drug metabolism">drug metabolism</a> at a specific location in the body which leads to a reduction in the <a href="/wiki/Concentration" title="Concentration">concentration</a> of the active <a href="/wiki/Drug" title="Drug">drug</a> before it reaches the site of action or systemic circulation.<sup id="cite_ref-Rowland1972_1-0" class="reference"><a href="#cite_note-Rowland1972-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-PondTozer1984_2-0" class="reference"><a href="#cite_note-PondTozer1984-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> The effect is most associated with <a href="/wiki/Orally_administered" class="mw-redirect" title="Orally administered">orally administered</a> <a href="/wiki/Medication" title="Medication">medications</a>, but some drugs still undergo first-pass metabolism even when delivered via an alternate route (e.g., <a href="/wiki/Intravenous_therapy" title="Intravenous therapy">IV</a>, <a href="/wiki/Intramuscular_injection" title="Intramuscular injection">IM</a>, etc.).<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> During this metabolism, drug is lost during the process of <a href="/wiki/Absorption_(pharmacology)" title="Absorption (pharmacology)">absorption</a> which is generally related to the <a href="/wiki/Liver" title="Liver">liver</a> and <a href="/wiki/Gut_wall" class="mw-redirect" title="Gut wall">gut wall</a>. The liver is the major site of first pass effect; however, it can also occur in the lungs, vasculature or other metabolically active tissues in the body. </p><p>Notable drugs that experience a significant first pass effect are <a href="/wiki/Buprenorphine" title="Buprenorphine">buprenorphine</a>, <a href="/wiki/Chlorpromazine" title="Chlorpromazine">chlorpromazine</a>, <a href="/wiki/Cimetidine" title="Cimetidine">cimetidine</a>, <a href="/wiki/Diazepam" title="Diazepam">diazepam</a>, <a href="/wiki/Alcohol_(drug)" title="Alcohol (drug)">ethanol</a> (drinking alcohol), <a href="/wiki/Imipramine" title="Imipramine">imipramine</a>, <a href="/wiki/Insulin_(medication)" title="Insulin (medication)">insulin</a>, <a href="/wiki/Lidocaine" title="Lidocaine">lidocaine</a>, <a href="/wiki/Midazolam" title="Midazolam">midazolam</a>, <a href="/wiki/Morphine" title="Morphine">morphine</a>, <a href="/wiki/Pethidine" title="Pethidine">pethidine</a>, <a href="/wiki/Propranolol" title="Propranolol">propranolol</a>, and <a href="/wiki/Tetrahydrocannabinol" title="Tetrahydrocannabinol">tetrahydrocannabinol</a> (THC). </p><p>First-pass metabolism is not to be confused with <a href="/wiki/Phase_I_metabolism" class="mw-redirect" title="Phase I metabolism">phase I metabolism</a>, which is a separate process. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Factors">Factors</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=First_pass_effect&action=edit&section=1" title="Edit section: Factors"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>First-pass metabolism may occur in the liver (for propranolol, lidocaine, <a href="/wiki/Clomethiazole" title="Clomethiazole">clomethiazole</a>, and nitroglycerin) or in the gut (for <a href="/wiki/Benzylpenicillin" title="Benzylpenicillin">benzylpenicillin</a> and <a href="/wiki/Insulin" title="Insulin">insulin</a>).<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> The four primary systems that affect the first pass effect of a drug are the <a href="/wiki/Enzyme" title="Enzyme">enzymes</a> of the <a href="/wiki/Gastrointestinal_tract" title="Gastrointestinal tract">gastrointestinal</a> <a href="/wiki/Lumen_(anatomy)" title="Lumen (anatomy)">lumen</a>,<sup id="cite_ref-:0_5-0" class="reference"><a href="#cite_note-:0-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> gastrointestinal wall enzymes,<sup id="cite_ref-:1_6-0" class="reference"><a href="#cite_note-:1-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> <sup id="cite_ref-:2_7-0" class="reference"><a href="#cite_note-:2-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> bacterial enzymes<sup id="cite_ref-:0_5-1" class="reference"><a href="#cite_note-:0-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> and hepatic enzymes.<sup id="cite_ref-:1_6-1" class="reference"><a href="#cite_note-:1-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:2_7-1" class="reference"><a href="#cite_note-:2-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Hepatic_first-pass">Hepatic first-pass</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=First_pass_effect&action=edit&section=2" title="Edit section: Hepatic first-pass"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>After a drug is swallowed, it is absorbed by the <a href="/wiki/Digestive_system" class="mw-redirect" title="Digestive system">digestive system</a> and enters the <a href="/wiki/Hepatic_portal_system" title="Hepatic portal system">hepatic portal system</a>. It is carried through the <a href="/wiki/Hepatic_portal_vein" class="mw-redirect" title="Hepatic portal vein">portal vein</a> into the <a href="/wiki/Liver" title="Liver">liver</a> before it reaches the rest of the body. The liver <a href="/wiki/Metabolism" title="Metabolism">metabolizes</a> many drugs, sometimes to such an extent that only a small amount of <a href="/wiki/Active_pharmaceutical_ingredient" class="mw-redirect" title="Active pharmaceutical ingredient">active drug</a> emerges from the liver to the rest of the <a href="/wiki/Circulatory_system" title="Circulatory system">circulatory system</a>. This <i>first pass</i> through the liver thus may greatly reduce the <a href="/wiki/Bioavailability" title="Bioavailability">bioavailability</a> of the drug. </p><p>An example of a drug where first-pass metabolism is a complication and disadvantage is in the antiviral drug <a href="/wiki/Remdesivir" title="Remdesivir">remdesivir</a>. Remdesivir cannot be administered orally because the entire dose would be trapped in the liver with little achieving systemic circulation or reaching target organs and cells (for example, cells infected with <a href="/wiki/SARS-CoV-2" title="SARS-CoV-2">SARS-CoV-2</a>).<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> For this reason, remdesivir is administered by IV infusion, bypassing the portal vein. However, significant hepatic extraction still occurs because of second pass metabolism, whereby a fraction of venous blood travels through the hepatic portal vein and hepatocytes. </p> <div class="mw-heading mw-heading2"><h2 id="Drug_design">Drug design</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=First_pass_effect&action=edit&section=3" title="Edit section: Drug design"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In <a href="/wiki/Drug_design" title="Drug design">drug design</a>, drug candidates may have good <a href="/wiki/Druglikeness" title="Druglikeness">druglikeness</a> but fail on first-pass metabolism because it is biochemically <a href="/wiki/Binding_selectivity" title="Binding selectivity">selective</a>.<sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Please_clarify" title="Wikipedia:Please clarify"><span title="The text near this tag is ambiguous, and needs clarification. (January 2024)">ambiguous</span></a></i>]</sup> <a href="/wiki/Physiologically_based_pharmacokinetic_modelling" title="Physiologically based pharmacokinetic modelling">Physiologically based pharmacokinetic models</a> (PBPK) are used to predict first-pass metabolism, although they require compound-specific adjustments due to variability in intestinal mucosal permeability and other factors.<sup id="cite_ref-:3_12-0" class="reference"><a href="#cite_note-:3-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:4_14-0" class="reference"><a href="#cite_note-:4-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Enzyme expression also varies between individuals, which may influence the efficiency of first-pass metabolism and thus the bioavailability of the drug.<sup id="cite_ref-:1_6-2" class="reference"><a href="#cite_note-:1-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Cytochrome_P450" title="Cytochrome P450">Cytochromes P450</a>, especially <a href="/wiki/CYP3A4" title="CYP3A4">CYP3A4</a>, play a crucial role in first-pass metabolism, affecting the bioavailability of drugs.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:3_12-1" class="reference"><a href="#cite_note-:3-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:4_14-1" class="reference"><a href="#cite_note-:4-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Mitigation">Mitigation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=First_pass_effect&action=edit&section=4" title="Edit section: Mitigation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Converting a drug into a <a href="/wiki/Prodrug" title="Prodrug">prodrug</a> can help avoid first-pass metabolism, thereby improving its bioavailability.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> In vitro models, such as the use of <a href="/wiki/Microfluidic_chips" class="mw-redirect" title="Microfluidic chips">microfluidic chips</a> that simulate the gut and liver, allow first-pass metabolism to be studied more accurately, facilitating the development of drugs with better absorption profiles.<sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Routes_of_administration">Routes of administration</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=First_pass_effect&action=edit&section=5" title="Edit section: Routes of administration"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Alternative <a href="/wiki/Route_of_administration" title="Route of administration">routes of administration</a>, such as <a href="/wiki/Insufflation_(medicine)" title="Insufflation (medicine)">insufflation</a>, <a href="/wiki/Rectal_administration" title="Rectal administration">rectal administration</a>,<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:5_21-0" class="reference"><a href="#cite_note-:5-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page: 5">: 5 </span></sup> <a href="/wiki/Intravenous" class="mw-redirect" title="Intravenous">intravenous</a>,<sup id="cite_ref-:5_21-1" class="reference"><a href="#cite_note-:5-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Pages: 4–5">: 4–5 </span></sup> <a href="/wiki/Intramuscular" class="mw-redirect" title="Intramuscular">intramuscular</a>, <a href="/wiki/Metered-dose_inhaler" title="Metered-dose inhaler">inhalational aerosol</a>, <a href="/wiki/Transdermal_patch" title="Transdermal patch">transdermal</a>, or <a href="/wiki/Sublingual" class="mw-redirect" title="Sublingual">sublingual</a>, avoid or partially avoid the first pass effect because they allow drugs to be absorbed directly into the <a href="/wiki/Systemic_circulation" class="mw-redirect" title="Systemic circulation">systemic circulation</a>.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> </p><p>Drugs with high first pass effect typically have a considerably higher oral dose than sublingual or <a href="/wiki/Parenteral" class="mw-redirect" title="Parenteral">parenteral</a> dose. There is marked individual variation in the oral dose due to differences in the extent of first-pass metabolism, frequently among several other factors. Oral bioavailability of many vulnerable drugs appears to be increased in patients with compromised liver function. Bioavailability is also increased if another drug competing for first-pass metabolism enzymes is given concurrently (e.g., propranolol and <a href="/wiki/Chlorpromazine" title="Chlorpromazine">chlorpromazine</a>). </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=First_pass_effect&action=edit&section=6" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/ADME" title="ADME">ADME</a>, an acronym in <a href="/wiki/Pharmacokinetics" title="Pharmacokinetics">pharmacokinetics</a> and <a href="/wiki/Pharmacology" title="Pharmacology">pharmacology</a> standing for absorption, distribution, metabolism, and excretion</li> <li><a href="/wiki/Biopharmaceutics_Classification_System" title="Biopharmaceutics Classification System">Biopharmaceutics Classification System</a></li> <li><a href="/wiki/Enteral_administration" title="Enteral administration">Enteral administration</a></li> <li><a href="/wiki/Partition_coefficient" title="Partition coefficient">Partition coefficient</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=First_pass_effect&action=edit&section=7" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-Rowland1972-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-Rowland1972_1-0">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFRowland1972" class="citation journal cs1">Rowland, Malcolm (January 1972). 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G.; Breimer, D. D. (1997-11-10). <a rel="nofollow" class="external text" href="https://linkinghub.elsevier.com/retrieve/pii/S0169409X97000744">"Hepatic first-pass effect and controlled drug delivery following rectal administration"</a>. <i>Advanced Drug Delivery Reviews</i>. 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First Pass Effect. 2022 Sep 24. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID 31869143.</li></ul>    </div><noscript><img src="https://login.wikimedia.org/wiki/Special:CentralAutoLogin/start?useformat=desktop&type=1x1&usesul3=0" alt="" width="1" height="1" style="border: none; position: absolute;"></noscript> <div class="printfooter" data-nosnippet="">Retrieved from "<a dir="ltr" href="https://en.wikipedia.org/w/index.php?title=First_pass_effect&oldid=1274619544">https://en.wikipedia.org/w/index.php?title=First_pass_effect&oldid=1274619544</a>"</div></div> <div id="catlinks" class="catlinks" data-mw="interface"><div id="mw-normal-catlinks" class="mw-normal-catlinks"><a href="/wiki/Help:Category" title="Help:Category">Categories</a>: <ul><li><a href="/wiki/Category:Pharmacokinetics" title="Category:Pharmacokinetics">Pharmacokinetics</a></li><li><a href="/wiki/Category:Medicinal_chemistry" title="Category:Medicinal chemistry">Medicinal chemistry</a></li></ul></div><div id="mw-hidden-catlinks" class="mw-hidden-catlinks mw-hidden-cats-hidden">Hidden categories: <ul><li><a href="/wiki/Category:Articles_with_short_description" title="Category:Articles with short description">Articles with short description</a></li><li><a href="/wiki/Category:Short_description_matches_Wikidata" title="Category:Short description matches Wikidata">Short description matches Wikidata</a></li><li><a href="/wiki/Category:Articles_needing_additional_references_from_December_2016" title="Category:Articles needing additional references from December 2016">Articles needing additional references from December 2016</a></li><li><a href="/wiki/Category:All_articles_needing_additional_references" title="Category:All articles needing additional references">All articles needing additional references</a></li><li><a href="/wiki/Category:Wikipedia_articles_needing_clarification_from_January_2024" title="Category:Wikipedia articles needing clarification from January 2024">Wikipedia articles needing clarification from January 2024</a></li><li><a href="/wiki/Category:Webarchive_template_wayback_links" title="Category:Webarchive template wayback links">Webarchive template wayback links</a></li></ul></div></div> </div> </main> </div> <div class="mw-footer-container"> <footer id="footer" class="mw-footer" > <ul id="footer-info"> <li id="footer-info-lastmod"> This page was last edited on 8 February 2025, at 11:12<span class="anonymous-show"> (UTC)</span>.</li> <li id="footer-info-copyright">Text is available under the <a href="/wiki/Wikipedia:Text_of_the_Creative_Commons_Attribution-ShareAlike_4.0_International_License" title="Wikipedia:Text of the Creative Commons Attribution-ShareAlike 4.0 International License">Creative Commons Attribution-ShareAlike 4.0 License</a>; additional terms may apply. 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