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Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions

Opioid analgesics remain a treatment option for refractory acute and chronic pain, despite their potential risk for abuse and adverse events (AEs). Opioids are associated with several common AEs, but the most bothersome is opioid-induced constipation (OIC). OIC is often overlooked but has the potent...

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Autores principales: Gudin, Jeffrey, Fudin, Jeffrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049282/
https://www.ncbi.nlm.nih.gov/pubmed/32158255
http://dx.doi.org/10.2147/JPR.S220859
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author Gudin, Jeffrey
Fudin, Jeffrey
author_facet Gudin, Jeffrey
Fudin, Jeffrey
author_sort Gudin, Jeffrey
collection PubMed
description Opioid analgesics remain a treatment option for refractory acute and chronic pain, despite their potential risk for abuse and adverse events (AEs). Opioids are associated with several common AEs, but the most bothersome is opioid-induced constipation (OIC). OIC is often overlooked but has the potential to affect patient quality of life, increase associated symptom burden, and impede long-term opioid compliance. The peripherally acting µ-receptor antagonists (PAMORAs) are a class of drugs that include methylnaltrexone, naloxegol, and naldemedine. Collectively, each is approved for the treatment of OIC. PAMORAs work peripherally in the gastrointestinal tract, without impacting the central analgesic effects of opioids. However, each has unique pharmacokinetic properties that may be impacted by coadministered drugs or food. This review focuses on important metabolic and pharmacokinetic principals that are pertinent to drug interactions involving µ-opioid receptor antagonists prescribed for OIC. It highlights subtle differences among the PAMORAs that may have clinical significance. For example, unlike naloxegol or naldemedine, methylnaltrexone is not a substrate for CYP3A4 or p-glycoprotein; therefore, its plasma concentration is not altered when coadministered with concomitant medications that are CYP3A4 or p-glycoprotein inducers or inhibitors. With a better understanding of pharmacokinetic nuances of each PAMORA, clinicians will be better equipped to identify potential safety and efficacy considerations that may arise when PAMORAs are coadministered with other medications.
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spelling pubmed-70492822020-03-10 Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions Gudin, Jeffrey Fudin, Jeffrey J Pain Res Review Opioid analgesics remain a treatment option for refractory acute and chronic pain, despite their potential risk for abuse and adverse events (AEs). Opioids are associated with several common AEs, but the most bothersome is opioid-induced constipation (OIC). OIC is often overlooked but has the potential to affect patient quality of life, increase associated symptom burden, and impede long-term opioid compliance. The peripherally acting µ-receptor antagonists (PAMORAs) are a class of drugs that include methylnaltrexone, naloxegol, and naldemedine. Collectively, each is approved for the treatment of OIC. PAMORAs work peripherally in the gastrointestinal tract, without impacting the central analgesic effects of opioids. However, each has unique pharmacokinetic properties that may be impacted by coadministered drugs or food. This review focuses on important metabolic and pharmacokinetic principals that are pertinent to drug interactions involving µ-opioid receptor antagonists prescribed for OIC. It highlights subtle differences among the PAMORAs that may have clinical significance. For example, unlike naloxegol or naldemedine, methylnaltrexone is not a substrate for CYP3A4 or p-glycoprotein; therefore, its plasma concentration is not altered when coadministered with concomitant medications that are CYP3A4 or p-glycoprotein inducers or inhibitors. With a better understanding of pharmacokinetic nuances of each PAMORA, clinicians will be better equipped to identify potential safety and efficacy considerations that may arise when PAMORAs are coadministered with other medications. Dove 2020-02-25 /pmc/articles/PMC7049282/ /pubmed/32158255 http://dx.doi.org/10.2147/JPR.S220859 Text en © 2020 Gudin and Fudin. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Gudin, Jeffrey
Fudin, Jeffrey
Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions
title Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions
title_full Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions
title_fullStr Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions
title_full_unstemmed Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions
title_short Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer on Pharmacokinetic Variabilities with a Focus on Drug Interactions
title_sort peripheral opioid receptor antagonists for opioid-induced constipation: a primer on pharmacokinetic variabilities with a focus on drug interactions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049282/
https://www.ncbi.nlm.nih.gov/pubmed/32158255
http://dx.doi.org/10.2147/JPR.S220859
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