Jump to content

Naloxegol

From Wikipedia, the free encyclopedia

Naloxegol
Clinical data
Trade namesMovantik, Moventig
Other namesNKTR-118
AHFS/Drugs.commovantik
License data
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokineticdata
Protein binding~4.2%
MetabolismLiver(CYP3A)
Eliminationhalf-life6–11 h
ExcretionFeces (68%), urine (16%)
Identifiers
  • (5α,6α)-4,5-epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)-17-(2-propen-1-yl)morphinan-3,14-diol
CAS Number
PubChemCID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC34H53NO11
Molar mass651.794g·mol−1
3D model (JSmol)
  • COCCOCCOCCOCCOCCOCCOCCO[C@H]1CC[C@]2([C@H]3Cc4ccc(c5c4[C@]2([C@H]1O5)CCN3CC=C)O)O
  • InChI=1S/C34H53NO11/c1-3-9-35-10-8-33-30-26-4-5-27(36)31(30)46-32(33)28(6-7-34(33,37)29(35)25-26)45-24-23-44-22-21-43-20-19-42-18-17-41-16-15-40-14-13-39-12-11-38-2/h3-5,28-29,32,36-37H,1,6-25H2,2H3/t28-,29+,32-,33-,34+/m0/s1
  • Key:XNKCCCKFOQNXKV-ZRSCBOBOSA-N

Naloxegol(INN;PEGylated naloxol;[4]trade namesMovantikandMoventig) is aperipherally acting μ-opioid receptor antagonistdeveloped byAstraZeneca,licensed fromNektar Therapeutics,for the treatment ofopioid-inducedconstipation.[5]It was approved in 2014 in adult patients with chronic, non-cancer pain.[6]Doses of 25 mg were found safe and well tolerated for 52 weeks.[7]When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.[8]

The most common side effects areabdominal pain,diarrhea,nausea,flatulence,vomiting,andheadache.[9]

Naloxegol was previously aSchedule IIdrug in the United States because of its chemical similarity to opium alkaloids. It was officially decontrolled in January 2015. It was reclassified as aprescription drugafter theFDAandDEAconcluded that theimpermeabilityof theblood–brain barrierto this compound made it non-habit-forming, and so without the potential forabuse.[10]

Medical use

[edit]

Naloxegol is indicated for the treatment ofopioid-induced constipation(OIC) in people with chronic non-cancer pain.[9][11]

Side effects

[edit]

The most common side effects areabdominal pain,diarrhea,nausea,flatulence,vomiting,andheadache.[9]

Pharmacodynamic properties

[edit]

Naloxegol inhibits opioid binding inμ-opioid receptorsin the gastrointestinal tract, thus decreasing the constipating effects (slowing of gastrointestinal motility and transit,hypertonicity,increased fluid reabsorption) associated withopioids.[12]

If naloxegol is coadministered with otheropioid antagonists,there is a potential for additive effect and increased risk ofopioid withdrawal.[9]

Mechanism of action

[edit]

Chemically, naloxegol is apegylated(polyethylene glycol-modified)derivativeof α-naloxol.Specifically, the 6-α-hydroxyl group of α-naloxolis connected via anetherlinkage to the freehydroxyl groupof a monomethoxy-terminated n=7oligomerofPEG,shown extending at the lower left of the molecule image at right. The "n=7" defines the number of two-carbon ethylenes, and so the chain length, of the attached PEG chain, and the "monomethoxy" indicates that the terminal hydroxyl group of the PEG is "capped" with amethyl group.[13]The pegylation of the 6-α-hydroxyl side chainofnaloxolprevents the drug from crossing theblood–brain barrier(BBB).[8]

References

[edit]
  1. ^"Prescription medicines: registration of new chemical entities in Australia, 2016".Therapeutic Goods Administration (TGA).21 June 2022.Retrieved10 April2023.
  2. ^"Health Canada New Drug Authorizations: 2015 Highlights".Health Canada.4 May 2016.Retrieved7 April2024.
  3. ^"Moventig EPAR".European Medicines Agency (EMA).8 December 2014.Retrieved28 September2024.
  4. ^Seifert R, Wieland T, Mannhold R, Kubinyi H, Folkers G (17 July 2006).G Protein-Coupled Receptors as Drug Targets: Analysis of Activation and Constitutive Activity.John Wiley & Sons. p. 227.ISBN978-3-527-60695-5.Retrieved14 May2012.
  5. ^"Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119".Archived fromthe originalon 13 February 2012.Retrieved14 May2012.
  6. ^"FDA approves MOVANTIK™ (naloxegol) Tablets C-II for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain".16 September 2014.Archivedfrom the original on 10 May 2015.
  7. ^Webster L, Chey WD, Tack J, Lappalainen J, Diva U, Sostek M (October 2014)."Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation"(PDF).Alimentary Pharmacology & Therapeutics.40(7): 771–9.doi:10.1111/apt.12899.PMID25112584.S2CID34286557.
  8. ^abGarnock-Jones KP (March 2015). "Naloxegol: a review of its use in patients with opioid-induced constipation".Drugs.75(4): 419–25.doi:10.1007/s40265-015-0357-2.PMID25666542.S2CID207488539.
  9. ^abcd"Movantik prescribing information highlights"(PDF).Retrieved14 August2019.
  10. ^"Schedules of Controlled Substances: Removal of Naloxegol From Control".www.deadiversion.usdoj.gov.Archivedfrom the original on 9 March 2016.Retrieved27 February2016.
  11. ^"Naloxegol for Opioid-Induced Constipation in Patients with Noncancer Pain"(PDF).
  12. ^Garnock-Jones KP (March 2015). "Naloxegol: a review of its use in patients with opioid-induced constipation".Drugs.75(4): 419–25.doi:10.1007/s40265-015-0357-2.PMID25666542.S2CID207488539.
  13. ^Technically, the molecule that is attached via the ether link isO-methyl-heptaethylene glycol [that is, methoxyheptaethylene glycol, CH3OCH2CH2O(CH2CH2O)5CH2CH2OH], molecular weight 340.4,CAS number4437-01-8. See"Compound Summary for CID 526555, Pubchem Compound 4437-01".PubChem Compound Database.Bethesda, MD:NCBI,U.S.NLM.2016.Archivedfrom the original on 5 February 2016.Retrieved28 January2016.