Naloxegol

Naloxegol
Clinical data
Trade names Movantik, Moventig
Synonyms NKTR-118
AHFS/Drugs.com movantik
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		 Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding ~4.2%
    Metabolism Hepatic (CYP3A)
    Elimination half-life 6–11 h
    Excretion Feces (68%), urine (16%)
    Identifiers
    CAS Number
    PubChem CID
    ChemSpider
    UNII
    KEGG
    ChEBI
    Chemical and physical data
    Formula C34H53NO11
    Molar mass 651.785 g/mol
    3D model (JSmol)

    Naloxegol (INN; PEGylated naloxol;[1] trade names Movantik and Moventig) is a peripherally selective opioid antagonist developed by AstraZeneca, licensed from Nektar Therapeutics, for the treatment of opioid-induced constipation.[2] It was approved in 2014 in adult patients with chronic, non-cancer pain.[3] Doses of 25 mg were found safe and well tolerated for 52 weeks.[4] When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.[5]

    Chemically, naloxegol is a pegylated (polyethylene glycol-modified) derivative of α-naloxol. Specifically, the 6-α-hydroxyl group of α-naloxol is connected via an ether linkage to the free hydroxyl group of a monomethoxy-terminated n=7 oligomer of PEG, 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 a methyl group.[6] The pegylation of the 6-α-hydroxyl side chain of naloxol prevents the drug from crossing the blood-brain barrier (BBB).[5] As such, it can be considered the antithesis of the peripherally-acting opiate loperamide which is utilized as an opiate-targeting anti-diarrheal agent that does not cause traditional opiate side-effects due to its inability to accumulate in the central nervous system in normal subjects.

    Naloxegol was previously a Schedule II drug in the United States because of its chemical similarity to opium alkaloids, but was recently reclassified as a prescription drug after the FDA concluded that the impermeability of the blood-brain barrier to this compound made it non-habit-forming, and so without the potential for abuse—specifically, naloxegol was officially decontrolled on 23 January 2015.[7]

    As a pure opioid antagonist Naloxegol has no potential for abuse.

    See also

    References and notes

    1. ↑ Roland Seifert; Thomas Wieland; Raimund Mannhold; Hugo Kubinyi; Gerd Folkers (17 July 2006). G Protein-Coupled Receptors as Drug Targets: Analysis of Activation and Constitutive Activity. John Wiley & Sons. p. 227. ISBN 978-3-527-60695-5. Retrieved 14 May 2012.
    2. ↑ "Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119". Archived from the original on 2012-02-13. Retrieved 2012-05-14.
    3. ↑ "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.
    4. ↑ "Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation". Aliment. Pharmacol. Ther. 40: 771–9. Oct 2014. doi:10.1111/apt.12899. PMID 25112584.
    5. 1 2 Garnock-Jones KP (2015). "Naloxegol: a review of its use in patients with opioid-induced constipation". Drugs. 75 (4): 419–425. doi:10.1007/s40265-015-0357-2.
    6. ↑ Technically, the molecule that is attached via the ether link is O-methyl-heptaethylene glycol [that is, methoxyheptaethylene glycol, CH3OCH2CH2O(CH2CH2O)5CH2CH2OH], molecular weight 340.4, CAS number 4437-01-8. See Pubchem Staff (2016). "Compound Summary for CID 526555, Pubchem Compound 4437-01". PubChem Compound Database. Bethesda, MD, USA: NCBI, U.S. NLM. Retrieved 28 January 2016.
    7. ↑ http://www.deadiversion.usdoj.gov/fed_regs/rules/2015/fr0123_3.htm


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