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641:"FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF VEKLURY® (remdesivir) FOR THE TREATMENT OF CORONAVIRUS DISEASE 2019 (COVID-19) IN PEDIATRIC PATIENTS WEIGHING 3.5 KG TO LESS THAN 40 KG OR PEDIATRIC PATIENTS LESS THAN 12 YEARS OF AGE WEIGHING AT LEAST 3.5 KG, WITH POSITIVE RESULTS OF DIRECT SARS-CoV-2 VIRAL TESTING WHO ARE: HOSPITALIZED, OR NOT HOSPITALIZED AND HAVE MILD-TO-MODERATE COVID-19, AND ARE AT HIGH RISK FOR PROGRESSION TO SEVERE COVID-19, INCLUDING HOSPITALIZATION OR DEATH"
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before it reaches the site of action or systemic circulation. The effect is most associated with orally administered medications, but some drugs still undergo first-pass metabolism even when delivered via an alternate route (e.g., IV, IM, etc.). During this metabolism, drug is lost during the process
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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
294:). 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.
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and gut wall. 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. Notable drugs that experience a significant first-pass effect are
290:. 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
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Herman TF, Santos C. First Pass Effect. 2022 Sep 24. In: StatPearls . Treasure Island (FL): StatPearls
Publishing; 2022 Jan–. PMID 31869143.
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increased if another drug competing for first pass metabolism enzymes is given concurrently (e.g., propranolol and
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An example of a drug where first pass metabolism is a complication and disadvantage is in the antiviral drug
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Drugs with high first pass effect typically have a considerably higher oral dose than sublingual or
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Rowland, Malcolm (January 1972). "Influence of route of administration on drug availability".
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593:"Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment"
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Pond, Susan M.; Tozer, Thomas N. (January 1984). "First-Pass
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at a specific location in the body which leads to a reduction in the
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Encyclopedia of
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standing for absorption, distribution, metabolism, and excretion
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564:Bath-Hextall, Fiona (October 16, 2013).
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566:"Understanding First Pass Metabolism"
65:adding citations to reliable sources
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572:from the original on July 28, 2021
536:10.1016/b978-0-12-823677-2.00086-6
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430:Journal of Pharmaceutical Sciences
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485:10.2165/00003088-198409010-00001
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678:Influence of Route of Exposure
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356:systemic circulation
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683:2010-06-11 at the
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551:2024-01-17
415:References
363:parenteral
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292:SARS-CoV-2
288:remdesivir
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