PMID- 32158255
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240328
IS  - 1178-7090 (Print)
IS  - 1178-7090 (Electronic)
IS  - 1178-7090 (Linking)
VI  - 13
DP  - 2020
TI  - Peripheral Opioid Receptor Antagonists for Opioid-Induced Constipation: A Primer 
      on Pharmacokinetic Variabilities with a Focus on Drug Interactions.
PG  - 447-456
LID - 10.2147/JPR.S220859 [doi]
AB  - 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 micro-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 micro-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.
CI  - (c) 2020 Gudin and Fudin.
FAU - Gudin, Jeffrey
AU  - Gudin J
AUID- ORCID: 0000-0002-2750-6488
AD  - Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ, USA.
AD  - Department of Anesthesiology, Englewood Hospital and Medical Center, Englewood, 
      NJ, USA.
FAU - Fudin, Jeffrey
AU  - Fudin J
AUID- ORCID: 0000-0001-9929-1909
AD  - Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
AD  - Western New England University College of Pharmacy, Springfield, MA, USA.
AD  - Remitigate, LLC, Delmar, NY, USA.
AD  - Stratton Veterans Affairs Medical Center, Albany, NY, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200225
PL  - New Zealand
TA  - J Pain Res
JT  - Journal of pain research
JID - 101540514
PMC - PMC7049282
OTO - NOTNLM
OT  - drug-related side effects and adverse reactions
OT  - opioid analgesics
OT  - opioid or opiate mu (micro)-receptor antagonists
OT  - pharmacokinetics; opioid-induced constipation
COIS- Jeffrey Gudin is part of the Advisory Board and/or Speakers Bureau for AcelRx 
      Pharmaceuticals, AstraZeneca, BioDelivery Sciences International, Daiichi Sankyo, 
      Scilex Pharmaceuticals, Salix Pharmaceuticals, and GlaxoSmithKline. He is a 
      consultant for Mallinckrodt, Nektar, and Quest Diagnostics. He is also an advisor 
      for Purdue. Jeffrey Fudin is part of Advisory Board and/or Speakers Bureau for 
      AcelRx Pharmaceuticals, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Quest 
      Diagnostics, Scilex Pharmaceuticals and Salix Pharmaceuticals. He is also a 
      speaker for Acutis Diagnostics, Inc and a consultant for Bio Delivery Sciences 
      International and Firstox Laboratories. The authors report no other conflicts of 
      interest in this work.
EDAT- 2020/03/12 06:00
MHDA- 2020/03/12 06:01
PMCR- 2020/02/25
CRDT- 2020/03/12 06:00
PHST- 2019/06/26 00:00 [received]
PHST- 2020/01/09 00:00 [accepted]
PHST- 2020/03/12 06:00 [entrez]
PHST- 2020/03/12 06:00 [pubmed]
PHST- 2020/03/12 06:01 [medline]
PHST- 2020/02/25 00:00 [pmc-release]
AID - 220859 [pii]
AID - 10.2147/JPR.S220859 [doi]
PST - epublish
SO  - J Pain Res. 2020 Feb 25;13:447-456. doi: 10.2147/JPR.S220859. eCollection 2020.