Editing First pass effect (section)

== Mitigation ==
Converting a drug into a [[prodrug]] can help avoid first-pass metabolism, thereby improving its bioavailability.<ref>{{Citation |last1=Shakya |first1=Ashok K. |title=Chapter 8 - First-Pass Metabolism Considerations in Pharmaceutical Product Development |date=2018-01-01 |work=Dosage Form Design Considerations |pages=259–286 |editor-last=Tekade |editor-first=Rakesh K. |url=https://linkinghub.elsevier.com/retrieve/pii/B9780128144237000083 |series=Advances in Pharmaceutical Product Development and Research |publisher=Academic Press |doi=10.1016/b978-0-12-814423-7.00008-3 |isbn=978-0-12-814423-7 |last2=Al-Najjar |first2=Belal O. |last3=Deb |first3=Pran Kishore |last4=Naik |first4=Rajashri R. |last5=Tekade |first5=Rakesh K.|url-access=subscription }}</ref> In vitro models, such as the use of [[microfluidic chips]] that simulate the gut and liver, allow first-pass metabolism to be studied more accurately, facilitating the development of drugs with better absorption profiles.<ref>{{Cite journal |last1=Lee |first1=Bo-Eun |last2=Kim |first2=Do-Kyung |last3=Lee |first3=Hyunil |last4=Yoon |first4=Siyeong |last5=Park |first5=Sin-Hyung |last6=Lee |first6=Soonchul |last7=Yoo |first7=Jongman |date=2021 |title=Recapitulation of First Pass Metabolism Using 3D Printed Microfluidic Chip and Organoid |journal=Cells |language=en |volume=10 |issue=12 |pages=3301 |doi=10.3390/cells10123301 |doi-access=free |issn=2073-4409 |pmc=8699265 |pmid=34943808}}</ref><ref>{{Cite journal |last1=Lee |first1=Dong Wook |last2=Ha |first2=Sang Keun |last3=Choi |first3=Inwook |last4=Sung |first4=Jong Hwan |date=2017-11-07 |title=3D gut-liver chip with a PK model for prediction of first-pass metabolism |url=https://link.springer.com/article/10.1007/s10544-017-0242-8 |journal=Biomedical Microdevices |language=en |volume=19 |issue=4 |pages=100 |doi=10.1007/s10544-017-0242-8 |issn=1572-8781|url-access=subscription }}</ref><ref>{{Cite journal |last1=Choe |first1=Aerim |last2=Ha |first2=Sang Keun |last3=Choi |first3=Inwook |last4=Choi |first4=Nakwon |last5=Sung |first5=Jong Hwan |date=2017-01-10 |title=Microfluidic Gut-liver chip for reproducing the first pass metabolism |url=https://link.springer.com/article/10.1007/s10544-016-0143-2 |journal=Biomedical Microdevices |language=en |volume=19 |issue=1 |pages=4 |doi=10.1007/s10544-016-0143-2 |pmid=28074384 |issn=1572-8781|url-access=subscription }}</ref>

=== Routes of administration ===
Alternative [[route of administration|routes of administration]], such as [[Insufflation (medicine)|insufflation]], [[rectal administration]],<ref>{{Cite journal |last1=de Boer |first1=A. G. |last2=Breimer |first2=D. D. |date=1997-11-10 |title=Hepatic first-pass effect and controlled drug delivery following rectal administration |url=https://linkinghub.elsevier.com/retrieve/pii/S0169409X97000744 |journal=Advanced Drug Delivery Reviews |series=Rectal Drug Delivery |volume=28 |issue=2 |pages=229–237 |doi=10.1016/S0169-409X(97)00074-4 |issn=0169-409X|url-access=subscription }}</ref><ref name=":5">{{Cite book |title=Aulton's Pharmaceutics: the design and manufacture of medicines |date=2022 |publisher=Elsevier Health Sciences |isbn=978-0-7020-8154-5 |editor-last=Taylor |editor-first=Kevin |edition=6th |location=s.l. |page=5 |chapter=Design of dosage forms |editor-last2=Aulton |editor-first2=Michael E.}}</ref>{{Rp|page=5}} [[intravenous]],<ref name=":5" />{{Rp|page=|pages=4-5}} [[intramuscular]], [[metered-dose inhaler|inhalational aerosol]], [[transdermal patch|transdermal]], or [[sublingual]], avoid or partially avoid the first pass effect because they allow drugs to be absorbed directly into the [[systemic circulation]].<ref>{{Cite journal |last1=Mathias |first1=Neil R. |last2=Hussain |first2=Munir A. |year=2009 |title=Non-invasive Systemic Drug Delivery: Developability Considerations for Alternate Routes of Administration |url=https://linkinghub.elsevier.com/retrieve/pii/S0022354916303525 |journal=Journal of Pharmaceutical Sciences |volume=99 |issue=1 |pages=1–20 |doi=10.1002/jps.21793 |pmid=19499570 |issn=0022-3549|url-access=subscription }}</ref>

Drugs with high first pass effect typically have a considerably higher oral dose than sublingual or [[parenteral]] 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 [[chlorpromazine]]).