Identification
- Generic Name
- Moxidectin
- DrugBank Accession Number
- DB11431
- Background
Moxidectin is a potent, broad-spectrum endectocide (antiparasitic that is active against endo- and ecto-parasites) with activity against nematodes, insects, and acari. It was first used in cattle followed by an approved use in general animals. It is a semi-synthetic methoxine derivative of nemadectin which is a 16-member pentacyclic lactone of the milbemycin class. Moxidectin differs by the absence of a disaccharide moiety on carbon 13, a substituted olefinic side chain at carbon 25 and a unique methoxime moiety at carbon 23. Due to these modifications, moxidectin is classified as a second generation macrocyclic lactone.1 Moxidectin was developed by Medicines Development for Global Health and FDA approved in June 13, 2018.7
- Type
- Small Molecule
- Groups
- Approved, Investigational, Vet approved
- Structure
Structure for Moxidectin (DB11431)
- Weight
- Average: 639.83
Monoisotopic: 639.377117671 - Chemical Formula
- C37H53NO8
- Synonyms
- Moxidectin
- Moxidectina
- Moxidectinum
- External IDs
- CL 301,423
- CL-301,423
- CL-301423
Pharmacology
- Indication
Moxidectin is indicated for the treatment of river blindness, also called onchocerciasis, in patients aged 12 years and older. River blindness is caused by a parasitic worm Onchocerca volvulus and it is manifested as severe itching, disfiguring skin conditions and visual impairment caused by the worm's larvae.8
The transmission of Onchocerca volvulus is performed person to person by black flies that breed in fast-flowing rivers in sub-Saharan Africa, Yemen and South and Central America. The larvae released by the adult parasite invade skin and eyes where they can produce the severe disease manifestations.8
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Onchocerciasis caused by infection with onchocerca volvulus •••••••••••• •••••• - Contraindications & Blackbox Warnings
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Moxidectin has been reported to be highly effective against Onchocerca volvulus when compared to ivermectin.3 When moxidectin was administered in infected individuals, the microfilarial load in the skin was lower even when compared to the current therapy, ivermectin. The levels of microfilarial got reduced to an undetectable level while being safe to be used in mass drug administration.9
- Mechanism of action
Moxidectin selectively binds to the parasite's GABA-A and glutamate-gated chloride ion channels which are vital for the function of invertebrate nerve and muscle cells. It presents activity against the parasite but it does not kill him.8 Once moxidectin is bound, there is an increased permeability leading to an influx of chloride ions and flaccid paralysis of the parasite.1
Target Actions Organism AGlutamate-gated chloride channel binderOnchocerca volvulus AGABA-A gated chloride channel binderOnchocerca volvulus NABC transporters binderOnchocerca volvulus - Absorption
The penetration of moxidectin in the parasite is not restricted as this compound is a very poor substrate of p-glycoprotein, which is vital for the reduction of the uptake of lipophilic compounds from the GI tract and for the increase in biliary, intestinal and renal secretion. After oral administration of moxidectin, the plasma maximal concentration of 70.4 mg/kg was reached after 0.37 day with a reported AUC of 363.6 mcg/day/ml.1 It is also important to mention that oral bioavailability is enhanced with the co-administration with lipids.6
- Volume of distribution
Moxidectin presents a larger volume of distribution and mean residence time when compared to ivermectin. The reported volume of distribution is of 1.2 l/kg.3
- Protein binding
This pharmacokinetic property in humans is unknown.Label
- Metabolism
Reports have registered enzymatic modification in humans and in nematodes. In the case of moxidectin, there has been registered C29-30- and C14-mono-hydroxymethyl derivatives mainly by the cytochrome CYP3A and CYP2B. The metabolism of moxidectin is considered to contribute to a small extent to the elimination.3 Some other metabolites formed are O-demethyl-dihydroxy metabolites. The metabolism of the of moxidectin is not major as the major residue in fat, liver, kidney and muscle is the unchanged moxidectin.5
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- Route of elimination
When moxidectin is orally administered, 2% of the dose is eliminated unchanged in the feces within 72 hours. Renal elimination is negligible.Label
- Half-life
Moxidectin reporter terminal half-life is 20.2 days.3
- Clearance
The apparent clearance of moxidectin is 3.5 L/hour.4
- Adverse Effects
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Moxidectin is reported to be safe as it is reported to be a poor substrate of P-glycoprotein.1 The reported LD50in mice are in the range of 70-131 micromol/kg.2 Carcinogenicity studies have not been performed. Moxidectin was shown to present no effects in genotoxicity, mutagenicity and fertility.Label The reports of overdose there are related to the presence of transient and self-limiting neurological signs including the presence of convulsions.11
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Moxidectin Tablet 2 mg/1 Oral Medicines Development for Global Health 2019-12-02 Not applicable US 
Moxidectin Tablet 2 mg/1 Oral Medicines Development for Global Health 2019-12-02 Not applicable US
Categories
- ATC Codes
- P02CX03 — Moxidectin
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as milbemycins. These are a group of macrolides with a structure containing a 16-membered lactone ring fused to a 1,7-dioxaspiroundecane ring system and to either a benzofuran (or hydrogenated derivative thereof). In some cases (e.g. Milbemycin E), the tetrahydrofuranyl ring is missing. Milbemycins can be o-glycosylated at C13 to form Avermectins. Milbemycins are produced by Streptomyces species.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Macrolides and analogues
- Sub Class
- Milbemycins
- Direct Parent
- Milbemycins
- Alternative Parents
- Ketals / Oxanes / Tetrahydrofurans / Tertiary alcohols / Secondary alcohols / Oxime ethers / Lactones / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives show 5 more
- Substituents
- Acetal / Alcohol / Aliphatic heteropolycyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dialkyl ether / Ether / Hydrocarbon derivative / Ketal show 16 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Microbes (bacteria, parasites)
Chemical Identifiers
- UNII
- NGU5H31YO9
- CAS number
- 113507-06-5
- InChI Key
- YZBLFMPOMVTDJY-LSGXYNIPSA-N
- InChI
- InChI=1S/C37H53NO8/c1-21(2)14-25(6)33-26(7)31(38-42-8)19-36(46-33)18-29-17-28(45-36)13-12-23(4)15-22(3)10-9-11-27-20-43-34-32(39)24(5)16-30(35(40)44-29)37(27,34)41/h9-12,14,16,21-22,26,28-30,32-34,39,41H,13,15,17-20H2,1-8H3/b10-9+,23-12+,25-14+,27-11+,38-31+/t22-,26-,28+,29-,30-,32+,33+,34+,36-,37+/m0/s1
- IUPAC Name
- (1'R,2R,4E,4'S,5S,6S,8'R,10'E,13'R,14'E,16'E,20'R,21'R,24'S)-21',24'-dihydroxy-4-(methoxyimino)-5,11',13',22'-tetramethyl-6-(4-methylpent-2-en-2-yl)-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1^{4,8}.0^{20,24}]pentacosane]-10',14',16',22'-tetraen-2'-one
- SMILES
- [H][C@@]12OC\C3=C/C=C/[C@H](C)C\C(C)=C\C[C@]4([H])C[C@@]([H])(C[C@]5(C\C(=N/OC)[C@H](C)[C@H](O5)C(\C)=C\C(C)C)O4)OC(=O)[C@]([H])(C=C(C)[C@H]1O)[C@@]23O
References
- General References
- Cobb R, Boeckh A: Moxidectin: a review of chemistry, pharmacokinetics and use in horses. Parasit Vectors. 2009 Sep 25;2 Suppl 2:S5. doi: 10.1186/1756-3305-2-S2-S5. [Article]
- Menez C, Sutra JF, Prichard R, Lespine A: Relative neurotoxicity of ivermectin and moxidectin in Mdr1ab (-/-) mice and effects on mammalian GABA(A) channel activity. PLoS Negl Trop Dis. 2012;6(11):e1883. doi: 10.1371/journal.pntd.0001883. Epub 2012 Nov 1. [Article]
- Prichard R, Menez C, Lespine A: Moxidectin and the avermectins: Consanguinity but not identity. Int J Parasitol Drugs Drug Resist. 2012 Apr 14;2:134-53. doi: 10.1016/j.ijpddr.2012.04.001. eCollection 2012 Dec. [Article]
- Korth-Bradley JM, Parks V, Chalon S, Gourley I, Matschke K, Gossart S, Bryson P, Fleckenstein L: Excretion of moxidectin into breast milk and pharmacokinetics in healthy lactating women. Antimicrob Agents Chemother. 2011 Nov;55(11):5200-4. doi: 10.1128/AAC.00311-11. Epub 2011 Sep 6. [Article]
- Brittain H. (2013). Profiles of drug substances and related methodology. Volume 38 (1st ed.). Elsevier. [ISBN:978-0-12-407691-4]
- Varga M. (2014). Textbook of rabbit medicine (2nd ed.). Butterworth Heinmann.
- FDA approval [Link]
- Pnswire [Link]
- Luxembourg Institute of Health [Link]
- FDA Approved Drug Products: Moxidectin for oral use [Link]
- EMA reports [File]
- External Links
- KEGG Drug
- D05084
- ChemSpider
- 22901017
- 1047072
- ChEMBL
- CHEMBL2104415
- ZINC
- ZINC000169649308
- Wikipedia
- Moxidectin
- FDA label
- Download (131 KB)
- MSDS
- Download (96.5 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Filariasis, Lymphatic 1 3 Active Not Recruiting Treatment Onchocerciasis 1 3 Completed Treatment Ascariasis / Hookworm Infections / Trichuriasis 1 3 Completed Treatment Onchocerciasis 1 3 Completed Treatment Strongyloides Stercoralis Infection 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Topical Tablet Oral 2 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 145-154 ºC 'MSDS' boiling point (°C) When found in oily form it is expected to boil at 160 ºC 'MSDS' water solubility Insoluble 'MSDS' logP 6 Menez C. et al. PLoS Negl Trop Dis. (2012) pKa 12.8 Brittain H. Profiles of Drug Substances, Excipients and Related Methodology. (2013) - Predicted Properties
Property Value Source Water Solubility 0.0052 mg/mL ALOGPS logP 5.3 ALOGPS logP 5.67 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 12.55 Chemaxon pKa (Strongest Basic) 2.81 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 116.04 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 179.22 m3·mol-1 Chemaxon Polarizability 71.02 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 261.21536 predictedDeepCCS 1.0 (2019) [M+H]+ 262.93912 predictedDeepCCS 1.0 (2019) [M+Na]+ 269.25494 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Onchocerca volvulus
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Extracellular ligand-gated ion channel activity
- Gene Name
- GluClX
- Uniprot ID
- Q25634
- Uniprot Name
- Glutamate-gated chloride channel
- Molecular Weight
- 40736.84 Da
References
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- This bond is implied based on in vitro animal studies and has not been confirmed otherwise.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Not Available
- Gene Name
- CYP2B
- Uniprot ID
- Q14097
- Uniprot Name
- CYP2B protein
- Molecular Weight
- 43147.81 Da
References
- Dupuy J, Escudero E, Eeckhoutte C, Sutra JF, Galtier P, Alvinerie M: In vitro metabolism of 14C-moxidectin by hepatic microsomes from various species. Vet Res Commun. 2001 Jul;25(5):345-54. doi: 10.1023/a:1010686508307. [Article]
Drug created at February 25, 2016 18:44 / Updated at February 21, 2021 18:53