Ivermectin

Basic Info

Common NameIvermectin(F05659)
2D Structure
FRCD IDF05659
CAS Number70161-11-4
PubChem CID6321424
FormulaC48H74O14
IUPAC Name

None

InChI Key

AZSNMRSAGSSBNP-XPNPUAGNSA-N

InChI

InChI=1S/C48H74O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3/b13-12+,27-15+,32-14+/t25-,26-,28-,30-,31-,33+,34-,35-,36-,37-,38-,39-,40+,41-,42-,43+,44-,45+,47+,48+/m0/s1

Canonical SMILES

CCC(C)C1C(CCC2(O1)CC3CC(O2)CC=C(C(C(C=CC=C4COC5C4(C(C=C(C5O)C)C(=O)O3)O)C)OC6CC(C(C(O6)C)OC7CC(C(C(O7)C)O)OC)OC)C)C

Isomeric SMILES

CC[C@H](C)[C@@H]1[C@H](CC[C@@]2(O1)C[C@@H]3C[C@H](O2)C/C=C(/[C@H]([C@H](/C=C/C=C/4\CO[C@H]5[C@@]4([C@@H](C=C([C@H]5O)C)C(=O)O3)O)C)O[C@H]6C[C@@H]([C@H]([C@@H](O6)C)O[C@H]7C[C@@H]([C@H]([C@@H](O7)C)O)OC)OC)\C)C

Synonyms
        
            IVERMECTIN
        
            Ivermectin B1a
        
            Dihydroavermectin B1a
        
            70288-86-7
        
            22,23-Dihydroavermectin B1a
        
            71827-03-7
        
            avermectin H2B1a
        
            UNII-91Y2202OUW
        
            70161-11-4
        
            CHEBI:63941
Classifies
                

                  
                    Veterinary Drug
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassPhenylpropanoids and polyketides
ClassMacrolides and analogues
SubclassMilbemycins
Intermediate Tree NodesNot available
Direct ParentMilbemycins
Alternative Parents
Molecular FrameworkAliphatic heteropolycyclic compounds
SubstituentsMilbemycin - Disaccharide - Glycosyl compound - O-glycosyl compound - Ketal - Oxane - Tetrahydrofuran - Tertiary alcohol - Carboxylic acid ester - Lactone - Secondary alcohol - Acetal - Carboxylic acid derivative - Dialkyl ether - Ether - Oxacycle - Organoheterocyclic compound - Monocarboxylic acid or derivatives - Organic oxide - Carbonyl group - Hydrocarbon derivative - Alcohol - Organic oxygen compound - Organooxygen compound - Aliphatic heteropolycyclic compound
DescriptionThis 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.

Properties

Property NameProperty Value
Molecular Weight875.106
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count14
Rotatable Bond Count8
Complexity1680
Monoisotopic Mass874.508
Exact Mass874.508
XLogP4.1
Formal Charge0
Heavy Atom Count62
Defined Atom Stereocenter Count20
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count3
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.5745
Human Intestinal AbsorptionHIA+0.9050
Caco-2 PermeabilityCaco2-0.7613
P-glycoprotein SubstrateSubstrate0.8316
P-glycoprotein InhibitorInhibitor0.7066
Inhibitor0.7394
Renal Organic Cation TransporterNon-inhibitor0.7382
Distribution
Subcellular localizationMitochondria0.8053
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8800
CYP450 2D6 SubstrateNon-substrate0.8855
CYP450 3A4 SubstrateSubstrate0.7739
CYP450 1A2 InhibitorNon-inhibitor0.9045
CYP450 2C9 InhibitorNon-inhibitor0.9071
CYP450 2D6 InhibitorNon-inhibitor0.9231
CYP450 2C19 InhibitorNon-inhibitor0.9025
CYP450 3A4 InhibitorNon-inhibitor0.8309
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.6859
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9533
Non-inhibitor0.5055
AMES ToxicityNon AMES toxic0.8174
CarcinogensNon-carcinogens0.9709
Fish ToxicityHigh FHMT0.9237
Tetrahymena Pyriformis ToxicityHigh TPT0.9989
Honey Bee ToxicityHigh HBT0.8752
BiodegradationNot ready biodegradable0.9584
Acute Oral ToxicityIII0.4494
Carcinogenicity (Three-class)Non-required0.5219
Model Value Unit
Absorption
Aqueous solubility-4.2367LogS
Caco-2 Permeability0.5354LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity3.5130LD50, mol/kg
Fish Toxicity0.5638pLC50, mg/L
Tetrahymena Pyriformis Toxicity1.1327pIGC50, ug/L

MRLs

FoodProduct CodeCountryMRLsApplication DateNotes
Muscle Of CattleUnited States10ppb
Muscle Of SwineUnited States20ppb
Liver Of American BisonUnited States15ppb
Liver Of ReindeerUnited States15ppb
Liver Of SheepUnited States30ppb
Liver Of SwineUnited States20ppb
Liver Of CattleUnited States100ppb
Other Poultry Animals,Edible OffalJapan0.02ppm
Chicken,Edible OffalJapan0.02ppm
Other Poultry Animals,KidneyJapan0.02ppm
Chicken,KidneyJapan0.02ppm
Other Poultry Animals,LiverJapan0.02ppm
Chicken,LiverJapan0.02ppm
Other Poultry Animals,FatJapan0.02ppm
Chicken,FatJapan0.02ppm
Other Poultry Animals,MuscleJapan0.01ppm
Chicken,MuscleJapan0.01ppm
MilkJapan0.01ppm
Horse,Edible OffalJapan0.01ppm
Sheep,Edible OffalJapan0.01ppm

References

TitleJournalDatePubmed ID
Pipette-tip solid-phase extraction using polypyrrole as efficient adsorbent forextraction of avermectins and milbemycins in milk.Anal Bioanal Chem2018 May29607449
Plasma dispositions and concentrations of ivermectin in eggs following treatment of laying hens.N Z Vet J2018 May29378154
Preparation and Characterization of Controlled-Release Avermectin/Castor Oil-Based Polyurethane Nanoemulsions.J Agric Food Chem2018 Jul 528562041
Effects of the Antiparasitic Drug Moxidectin in Cattle Dung on Zooplankton and Benthic Invertebrates and its Accumulation in a Water-Sediment System.Arch Environ Contam Toxicol2018 Aug29846763
Residue depletion of ivermectin in broiler poultry.Food Addit Contam Part A Chem Anal Control Expo Risk Assess2017Apr28067137
Relationship between ivermectin concentrations at the injection site, muscle and fat of steers treated with traditional and long-acting preparations.Food Chem Toxicol2017 Jul28479392
Caprine ovarian follicle requirements differ between preantral and early antralstages after IVC in medium supplemented with GH and VEGF alone or in combination.Theriogenology2017 Jan 127729112
P-glycoproteins play a role in ivermectin resistance in cyathostomins.Int J Parasitol Drugs Drug Resist2017 Dec29121562
The development of an ivermectin-based attractive toxic sugar bait (ATSB) to target Anopheles arabiensis.Malar J2017 Aug 1528810866
Accelerated follicle growth during the culture of isolated caprine preantralfollicles is detrimental to follicular survival and oocyte meiotic resumption.Theriogenology2016 Oct 127371972
Multiresidue method for simultaneous analysis of aflatoxin M1, avermectins, organophosphate pesticides and milbemycin in milk by ultra-performance liquid chromatography coupled to tandem mass spectrometry.Food Addit Contam Part A Chem Anal Control Expo Risk Assess2016 Jun27144891
Eco-toxicological effects of the avermectin family with a focus on abamectin and ivermectin.Chemosphere2016 Jul27058912
The physiological consequences of ingesting a toxic plant (Diplotaxis tenuifolia) influence subsequent foraging decisions by sheep (Ovis aries).Physiol Behav2016 Dec 127650920
Comparative plasma and milk dispositions, faecal excretion and efficacy of per osivermectin and pour-on eprinomectin in horses.J Vet Pharmacol Ther2016 Dec27016093
Oral delivery of ivermectin using a fast dissolving oral film: Implications forrepurposing ivermectin as a pharmacotherapy for alcohol use disorder.Alcohol2015 Sep26095588
Surveillance at the molecular level: Developing an integrated network fordetecting variation in avian influenza viruses in Indonesia.Prev Vet Med2015 Jun 125772529
Effect of high fat intake on the pharmacokinetic profile of ivermectin inrabbits.Drug Metab Pharmacokinet2015 Jun25887422
Ivermectin Pharmacokinetics, Metabolism, and Tissue/Egg Residue Profiles inLaying Hens.J Agric Food Chem2015 Dec 226553292
Anthelmintic resistance in gastrointestinal nematodes from grazing beef cattle inCampeche State, Mexico.Trop Anim Health Prod2015 Aug25876195
Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.Neuroreport2014 Sep 1025004078