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Identification
NameIvermectin
Accession NumberDB00602  (APRD01058)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

Ivermectin is a broad-spectrum anti-parasite medication. It was first marketed under the name Stromectol® and used against worms (except tapeworms), but, in 2012, it was approved for the topical treatment of head lice infestations in patients 6 months of age and older, and marketed under the name Sklice™ as well. Ivermectin is mainly used in humans in the treatment of onchocerciasis, but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis).

Structure
Thumb
Synonyms
Ivermectin
Ivermectina
Ivermectine
Ivermectinum
External Identifiers
  • MK 933
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Rosivercream1 %topicalGalderma Canada Inc2015-05-25Not applicableCanada
Sklicelotion.585 g/117gtopicalSanofi Pasteur, Inc2012-07-09Not applicableUs
Soolantracream10 mg/gtopicalGalderma Laboratories, L.P.2015-01-01Not applicableUs
Stromectoltablet3 mg/1oralMerck Sharp & Dohme Corp.1996-11-22Not applicableUs
Stromectoltablet3 mg/1oralDepartment Of State Health Services, Pharmacy Branch1996-11-22Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ivermectintablet3 mg/1oralEdenbridge Pharmaceuticals, LLC2014-11-15Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AscapilAbbott
DetebencilRoux-Ocefa
ErmetinUnipharm
GotaxMetlen
ImectinPulse
IvectinAristopharma
IveraBeximco
IvergotLicol
IvermecUCI
IvextermValeant
IvoriInvision
KaonolMediderm
KiloxBussié
MaikedingHisun
QuanoxDermacare
RevectinaSolvay
ScaboDelta
ScavistaZuventus
SecuroValeant
VermectinAtlantic Lab
Brand mixturesNot Available
SaltsNot Available
Categories
UNII8883YP2R6D
CAS number70288-86-7
WeightAverage: 1736.1589
Monoisotopic: 1735.000064088
Chemical FormulaC95H146O28
InChI KeyInChIKey=SPBDXSGPUHCETR-CVSKBELMSA-N
InChI
InChI=1S/C48H74O14.C47H72O14/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;1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-13-31-23-54-44-39(48)28(6)18-34(45(50)57-33)47(31,44)51)58-38-21-36(53-10)43(30(8)56-38)59-37-20-35(52-9)40(49)29(7)55-37/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3;11-14,18,24-25,27,29-30,32-44,48-49,51H,15-17,19-23H2,1-10H3/b13-12+,27-15+,32-14+;12-11+,26-14+,31-13+/t25-,26+,28+,30+,31+,33-,34+,35+,36+,37+,38+,39+,40-,41+,42+,43-,44+,45-,47-,48-;25-,27-,29-,30-,32+,33-,34-,35-,36-,37-,38-,39+,40-,41+,42-,43-,44+,46+,47+/m10/s1
IUPAC Name
(1'R,2R,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-6-(propan-2-yl)-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one; (1'R,2R,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-6-[(2R)-butan-2-yl]-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one
SMILES
CO[[email protected]]1C[C@@H](O[C@@H](C)[C@@H]1O)O[[email protected]]1[[email protected]](C)O[[email protected]](C[C@@H]1OC)O[[email protected]]1[C@@H](C)\C=C\C=C2/CO[C@@H]3[[email protected]](O)C(C)=C[C@@H](C(=O)O[[email protected]]4C[C@@H](C\C=C1/C)O[C@@]1(CC[[email protected]](C)[C@@H](C(C)C)O1)C4)[C@]23O.CC[C@@H](C)[[email protected]]1O[C@@]2(CC[C@@H]1C)O[C@@H]1C\C=C(C)\[C@@H](O[C@@H]3O[C@@H](C)[[email protected]](O[C@@H]4O[C@@H](C)[[email protected]](O)[C@@H](OC)C4)[C@@H](OC)C3)[C@@H](C)\C=C\C=C3/CO[C@@H]4[[email protected]](O)C(C)=C[C@@H](C(=O)O[C@@H](C1)C2)[C@]34O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as macrolides and analogues. These are organic compounds containing a lactone ring of at least twelve members.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolides and analogues
Sub ClassNot Available
Direct ParentMacrolides and analogues
Alternative Parents
Substituents
  • Macrolide
  • Oxane
  • Monosaccharide
  • Saccharide
  • Tertiary alcohol
  • Oxolane
  • Secondary alcohol
  • Lactone
  • Carboxylic acid ester
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of intestinal (i.e., nondisseminated) strongyloidiasis due to the nematode parasite Strongyloides stercoralis. Also for the treatment of onchocerciasis (river blindness) due to the nematode parasite Onchocerca volvulus. Can be used to treat scabies caused by Sarcoptes scabiei.
PharmacodynamicsIvermectin is a semisynthetic, anthelminitic agent. It is an avermectin which a group of pentacyclic sixteen-membered lactone (i.e. a macrocyclic lactone disaccharide) derived from the soil bacterium Streptomyces avermitilis. Avermectins are potent anti-parasitic agents. Ivermectin is the most common avermectin. It is a broad spectrum antiparasitic drug for oral administration. It is sometimes used to treat human onchocerciasis (river blindness). It is the mixture of 22,23-dihydro-avermectin B1a (at least 90%) and 22,23-dihydro-avermectin B1b (less than 10%).
Mechanism of actionIvermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms.
Related Articles
AbsorptionModerately well absorbed. Improved absorption with high fat meal.
Volume of distribution

The volume of distribution is 3 to 3.5 L/kg and it does not cross the blood-brain barrier.

Protein binding93%
Metabolism

Primarily hepatic. Ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1 % of the administered dose excreted in the urine.

Route of eliminationIvermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine.
Half life16 hours (also reported at 22-28 hours)
ClearanceNot Available
ToxicityLD50 = 29.5 mg/kg (Mouse, oral). LD50 = 10 mg/kg (Rat, oral). Adverse effects include muscle or joint pain, dizziness, fever, headache, skin rash, fast heartbeat.
Affected organisms
  • Parasitic nematodes and other roundworms
  • Head lice
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8146
Blood Brain Barrier-0.549
Caco-2 permeable-0.8192
P-glycoprotein substrateSubstrate0.8771
P-glycoprotein inhibitor IInhibitor0.805
P-glycoprotein inhibitor IIInhibitor0.8192
Renal organic cation transporterNon-inhibitor0.7384
CYP450 2C9 substrateNon-substrate0.8877
CYP450 2D6 substrateNon-substrate0.886
CYP450 3A4 substrateSubstrate0.7714
CYP450 1A2 substrateNon-inhibitor0.9129
CYP450 2C9 inhibitorNon-inhibitor0.8366
CYP450 2D6 inhibitorNon-inhibitor0.928
CYP450 2C19 inhibitorNon-inhibitor0.8793
CYP450 3A4 inhibitorNon-inhibitor0.7957
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8073
Ames testNon AMES toxic0.8295
CarcinogenicityNon-carcinogens0.9622
BiodegradationNot ready biodegradable0.9759
Rat acute toxicity3.5285 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9471
hERG inhibition (predictor II)Non-inhibitor0.5536
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers
Dosage forms
FormRouteStrength
Creamtopical1 %
Lotiontopical.585 g/117g
Creamtopical10 mg/g
Tabletoral3 mg/1
Prices
Unit descriptionCostUnit
Stromectol 20 3 mg tablet Box116.13USD box
Ivermectin powder14.0USD g
Stromectol 3 mg tablet5.58USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5952372 No1998-09-182018-09-18Us
US6103248 No1998-05-222018-05-22Us
US6133310 No1999-04-262019-04-26Us
US7550440 No2004-04-222024-04-22Us
US8080530 No2004-04-222024-04-22Us
US8093219 No2004-04-222024-04-22Us
US8415311 No2004-04-222024-04-22Us
US8470788 No2004-04-222024-04-22Us
US8791153 No2007-10-122027-10-12Us
US8815816 No2004-04-222024-04-22Us
US8927595 No2007-10-122027-10-12Us
US9089587 No2014-03-132034-03-13Us
US9233117 No2014-03-132034-03-13Us
US9233118 No2014-03-132034-03-13Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point155 °CNot Available
water solubilityInsolubleNot Available
Predicted Properties
PropertyValueSource
logP5.83ChemAxon
pKa (Strongest Acidic)12.47ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area170.06 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity230.33 m3·mol-1ChemAxon
Polarizability96.87 Å3ChemAxon
Number of Rings14ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Shuet-Hing L. Chiu, Josephine R. Carlin, Rae Taub, “Ivermectin derivative compounds and process for preparing the same.” U.S. Patent US4963667, issued June, 1982.

US4963667
General ReferencesNot Available
External Links
ATC CodesD11AX22P02CF01
AHFS Codes
  • 8:08
PDB EntriesNot Available
FDA labelDownload (60.2 KB)
MSDSDownload (73.4 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolIvermectin may increase the anticoagulant activities of Acenocoumarol.
AzithromycinThe serum concentration of Ivermectin can be increased when it is combined with Azithromycin.
DicoumarolIvermectin may increase the anticoagulant activities of Dicoumarol.
LumacaftorThe serum concentration of Ivermectin can be decreased when it is combined with Lumacaftor.
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Ivermectin.
RanolazineThe serum concentration of Ivermectin can be increased when it is combined with Ranolazine.
SaquinavirThe serum concentration of Ivermectin can be increased when it is combined with Saquinavir.
TesmilifeneThe serum concentration of Ivermectin can be decreased when it is combined with Tesmilifene.
VerapamilThe serum concentration of Ivermectin can be increased when it is combined with Verapamil.
WarfarinIvermectin may increase the anticoagulant activities of Warfarin.
Food Interactions
  • When administered with a high fat meal, the bioavailability is increased 2.5 times.

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Gaba-gated chloride ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB3
Uniprot ID:
P28472
Molecular Weight:
54115.04 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  2. Feng XP, Hayashi J, Beech RN, Prichard RK: Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. J Neurochem. 2002 Nov;83(4):870-8. [PubMed:12421359 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA3
Uniprot ID:
O75311
Molecular Weight:
53799.775 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  2. Yates DM, Wolstenholme AJ: An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria immitis. Int J Parasitol. 2004 Aug;34(9):1075-81. [PubMed:15313134 ]
  3. McCavera S, Rogers AT, Yates DM, Woods DJ, Wolstenholme AJ: An ivermectin-sensitive glutamate-gated chloride channel from the parasitic nematode Haemonchus contortus. Mol Pharmacol. 2009 Jun;75(6):1347-55. doi: 10.1124/mol.108.053363. Epub 2009 Mar 31. [PubMed:19336526 ]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389 ]
  2. Pouliot JF, L'Heureux F, Liu Z, Prichard RK, Georges E: Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. Biochem Pharmacol. 1997 Jan 10;53(1):17-25. [PubMed:8960059 ]
  3. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103 ]
  4. Schinkel AH, Wagenaar E, van Deemter L, Mol CA, Borst P: Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest. 1995 Oct;96(4):1698-705. [PubMed:7560060 ]
  5. Jani M, Makai I, Kis E, Szabo P, Nagy T, Krajcsi P, Lespine A: Ivermectin interacts with human ABCG2. J Pharm Sci. 2011 Jan;100(1):94-7. doi: 10.1002/jps.22262. Epub 2010 Jun 22. [PubMed:20574995 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. Lespine A, Dupuy J, Orlowski S, Nagy T, Glavinas H, Krajcsi P, Alvinerie M: Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3). Chem Biol Interact. 2006 Feb 25;159(3):169-79. Epub 2005 Dec 27. [PubMed:16384552 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Lespine A, Dupuy J, Orlowski S, Nagy T, Glavinas H, Krajcsi P, Alvinerie M: Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3). Chem Biol Interact. 2006 Feb 25;159(3):169-79. Epub 2005 Dec 27. [PubMed:16384552 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Jani M, Makai I, Kis E, Szabo P, Nagy T, Krajcsi P, Lespine A: Ivermectin interacts with human ABCG2. J Pharm Sci. 2011 Jan;100(1):94-7. doi: 10.1002/jps.22262. Epub 2010 Jun 22. [PubMed:20574995 ]
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Drug created on June 13, 2005 07:24 / Updated on May 27, 2016 02:18