Ivermectin
|
| Systematic (IUPAC) name |
| 22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b |
| Clinical data |
| Trade names |
Stromectol |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a607069 |
| Pregnancy cat. |
B3 (AU) C (US) |
| Legal status |
℞-only (US) |
| Routes |
Oral |
| Pharmacokinetic data |
| Protein binding |
93% |
| Metabolism |
Liver (CYP450) |
| Half-life |
18 hours |
| Excretion |
Feces; <1% urine |
| Identifiers |
| CAS number |
70288-86-7 Y 71827-03-7 |
| ATC code |
P02CF01 QP54AA01 QS02QA03 |
| PubChem |
CID 9812710 |
| DrugBank |
APRD01058 |
| ChemSpider |
7988461 Y |
| UNII |
8883YP2R6D Y |
| KEGG |
D00804 Y |
| ChEMBL |
CHEMBL341047 N |
| Chemical data |
| Formula |
C48H74O14 (22,23-dihydroavermectin B1a)
C47H72O14 (22,23-dihydroavermectin B1b) |
| Mol. mass |
875.10 g/mol |
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+/m00/s1 Y
Key:SPBDXSGPUHCETR-JFUDTMANSA-N Y
|
N (what is this?) (verify)
|
Ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b) is a broad-spectrum antiparasitic avermectin medicine. It is sold under brand names Sklice and Stromectol in the United States, Ivomec in Europe by Merial Animal Health, Mectizan in Canada by Merck and Ivexterm in Mexico by Valeant Pharmaceuticals International. In southeast Asian countries like Bangladesh, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6. While in development, it was assigned the code MK-933 by Merck.[1]
Contents
- 1 Uses
- 1.1 Helminth
- 1.2 Arthropod
- 1.3 Veterinary use
- 2 Pharmacology
- 2.1 Pharmacodynamics
- 2.2 Pharmacokinetics
- 2.3 Toxicity and potential drug interactions
- 2.4 Ecotoxicity
- 3 Contraindications
- 4 Discovery
- 5 Note and references
- 6 See also
- 7 External links
Uses[edit]
Ivermectin is a broad-spectrum antiparasitic agent.
Helminth[edit]
It is traditionally used against worms.
It is mainly used in humans in the treatment of onchocerciasis, but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis, filariasis, enterobiasis, and some epidermal parasitic skin diseases, including scabies.
Ivermectin, under the brand name Mectizan, is currently being used to help eliminate river blindness (onchocerciasis) in the Americas, and to stop transmission of lymphatic filariasis and onchocerciasis around the world.[2][3][4] Currently, large amounts of ivermectin are donated by Merck to fight river blindness in countries unable to afford the drug.[5] The disease is endemic in 30 African countries, six Latin American countries, and Yemen, according to studies conducted by the World Health Organization.[6] The drug rapidly kills microfilariae, but not the adult worms. A single oral dose of ivermectin, taken annually for the 10- to 15-year lifespan of the adult worms, is all that is needed to protect the individual from onchocerciasis.[7]
Arthropod[edit]
More recent evidence supports its off-label use against arthropods:
- Mites such as scabies:[8][9][10] It is usually limited to cases that prove to be resistant to topical treatments or which present in an advanced state (such as Norwegian scabies).[10]
- Lice:[11][12] Ivermectin lotion (0.5%) is FDA approved for patients six months of age and older.[13] After a single, 10-minute application of this formulation on dry hair, 78% of subjects were found to be free of lice after two weeks.[14] This level of effectiveness is equivalent to other pediculicide treatments requiring two applications.[15]
- Bed bugs:[16] Early research shows that the drug kills bed bugs when taken by humans at normal doses. The drug enters the human bloodstream and if the bedbugs bite during that time, the bedbug will die in a few days.
Veterinary use[edit]
Ivermectin is also used in veterinary medicine. It is sometimes administered in combination with other medications to treat a broad spectrum of animal parasites. Some dog breeds (especially the Rough Collie, the Smooth Collie, the Shetland Sheepdog, and the Australian Shepherd), though, have a high incidence of a certain mutation within the MDR1 gene; affected animals are particularly sensitive to the toxic effects of ivermectin.[17] Clinical evidence suggests kittens are susceptible to ivermectin toxicity.[18] A 0.01% ivermectin topical preparation for treating ear mites in cats (Acarexx) is available.
Ivermectin is sometimes used as an acaricide in reptiles, both by injection and as a diluted spray. While this works well in some cases, care must be taken, as several species of reptiles are very sensitive to ivermectin. Use in turtles is particularly contraindicated.
Pharmacology[edit]
Pharmacodynamics[edit]
Ivermectin and other avermectins (insecticides most frequently used in home-use ant baits) are macrocyclic lactones derived from the bacterium Streptomyces avermitilis. Ivermectin kills by interfering with nervous system and muscle function, in particular by enhancing inhibitory neurotransmission.
The drug binds and activates glutamate-gated chloride channels (GluCls).[19] GluCls are invertebrate-specific members of the Cys-loop family of ligand-gated ion channels present in neurons and myocytes.
Pharmacokinetics[edit]
Ivermectin can be given either by mouth or injection. It does not readily cross the blood–brain barrier of mammals due to the presence of P-glycoprotein,[20] although crossing may still become significant if it is given at high doses (in which case, brain levels peak 2–5 hr after administration). In contrast to mammals, ivermectin can cross the blood–brain barrier in tortoises, often with fatal consequences.
Toxicity and potential drug interactions[edit]
The main concern is neurotoxicity, which in most mammalian species may manifest as central nervous system depression, and consequent ataxia, as might be expected from potentiation of inhibitory GABA-ergic synapses.
Dogs with defects in the P-glycoprotein gene can be severely poisoned by ivermectin.
Since drugs that inhibit CYP3A4 enzymes often also inhibit P-glycoprotein transport, the risk of increased absorption past the blood-brain barrier exists when ivermectin is administered along with other CYP3A4 inhibitors. These drugs include statins, HIV protease inhibitors, many calcium channel blockers, the glucocorticoids such as dexamethasone, lidocaine, and the benzodiazepines.[21]
For dogs, the insecticide spinosad may have the effect of increasing the potency of ivermectin.[22]
Ecotoxicity[edit]
Field studies have demonstrated the dung of animals treated with ivermectin supports a significantly reduced diversity of invertebrates, and the dung persists longer.[23]
Contraindications[edit]
Ivermectin is contraindicated in children under the age of five, or those who weigh less than 15 kg (33 lb);[24] and those who are breastfeeding, and have a hepatic or renal disease.[25]
Discovery[edit]
The discovery of the avermectin family of compounds, from which ivermectin is chemically derived, was made by a team of scientists at Merck Institute for Therapeutic Research. A large international program of development resulted in the introduction of ivermectin as a commercial antiparasitic agent in 1981.[26]
Note and references[edit]
- ^ Pampiglione S, Majori G, Petrangeli G, Romi R (1985). "Avermectins, MK-933 and MK-936, for mosquito control". Trans R Soc Trop Med Hyg 79 (6): 797–9. doi:10.1016/0035-9203(85)90121-X. PMID 3832491.
- ^ The Carter Center. "River Blindness (Onchocerciasis) Program". Retrieved 2008-07-17 .
- ^ The Carter Center. "Lymphatic Filariasis Elimination Program". Retrieved 2008-07-17 .
- ^ WHO. accessdate=2009-11-12 "African Programme for Onchocerciasis Control" .
- ^ http://www.mectizan.org/about
- ^ United Front Against Riverblindness. "Onchocerciasis or Riverblindness" .
- ^ United Front Against Riverblindness. "Control of Riverblindness" .
- ^ Brooks PA, Grace RF (August 2002). "Ivermectin is better than benzyl benzoate for childhood scabies in developing countries". J Paediatr Child Health 38 (4): 401–4. doi:10.1046/j.1440-1754.2002.00015.x. PMID 12174005.
- ^ Victoria J, Trujillo R (2001). "Topical ivermectin: a new successful treatment for scabies". Pediatr Dermatol 18 (1): 63–5. doi:10.1046/j.1525-1470.2001.018001063.x. PMID 11207977.
- ^ a b Strong M, Johnstone PW (2007). "Interventions for treating scabies". In Strong, Mark. Cochrane Database of Systematic Reviews (Online) (3): CD000320. doi:10.1002/14651858.CD000320.pub2. PMID 17636630.
- ^ Dourmishev AL, Dourmishev LA, Schwartz RA (December 2005). "Ivermectin: pharmacology and application in dermatology". International Journal of Dermatology 44 (12): 981–8. doi:10.1111/j.1365-4632.2004.02253.x. PMID 16409259.
- ^ Strycharz JP, Yoon KS, Clark JM (January 2008). "A new ivermectin formulation topically kills permethrin-resistant human head lice (Anoplura: Pediculidae)". Journal of Medical Entomology 45 (1): 75–81. doi:10.1603/0022-2585(2008)45[75:ANIFTK]2.0.CO;2. ISSN 0022-2585. PMID 18283945.
- ^ "Sklice lotion".
- ^ David M. Pariser, M.D., Terri Lynn Meinking, Ph.D., Margie Bell, M.S., and William G. Ryan, B.V.Sc. (November 1, 2012). "Topical 0.5% Ivermectin Lotion for Treatment of Head Lice". New England Journal of Medicine 367: 1687–1693.
- ^ Study shows Ivermectin ending lice problem in one treatment, Los Angeles Times, Nov 5, 2012
- ^ DONALD G. MCNEIL JR. (2012-12-31). "Pill Could Join Arsenal Against Bedbugs". The New York Times. Retrieved 2013-04-05.
- ^ "MDR1 FAQs", Australian Shepherd Health & Genetics Institute, Inc.
- ^ Frischke H, Hunt L (April 1991). "Suspected ivermectin toxicity". Canadian Veterinary Journal 32 (4): 245. PMC 1481314. PMID 17423775.
- ^ Yates DM, Wolstenholme AJ (August 2004). "An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria immitis". Int. J. Parasitol. 34 (9): 1075–81. doi:10.1016/j.ijpara.2004.04.010. PMID 15313134.
- ^ Borst P, Schinkel AH (June 1996). "What have we learnt thus far from mice with disrupted P-glycoprotein genes?". European Journal of Cancer 32 (6): 985–990. doi:10.1016/0959-8049(96)00063-9.
- ^ Goodman and Gilman's Pharmacological Basis of Therapeutics, 11th edition, pages 122, 1084-1087.
- ^ "COMFORTIS® and ivermectin interaction Safety Warning Notification". U.S. Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM).
- ^ Iglesias LE, Saumell CA, Fernández AS, et al. (December 2006). "Environmental impact of ivermectin excreted by cattle treated in autumn on dung fauna and degradation of faeces on pasture". Parasitology Research 100 (1): 93–102. doi:10.1007/s00436-006-0240-x. PMID 16821034.
- ^ Dourmishev AL, Dourmishev LA, Schwartz RA (December 2005). "Ivermectin: pharmacology and application in dermatology". International Journal of Dermatology 44 (12): 981–988. doi:10.1111/j.1365-4632.2004.02253.x. PMID 16409259.
- ^ Huukelbach J, Winter B, Wilcke T, "et al." (August 2004). "Tratmient masivo selectivo con ivermectina contra las helmintiasis intestinales y parasitos cutáneas en una población gravemente afectada". Bull World Health Organ 82 (7): 563–571. doi:10.1590/S0042-96862004000800005.
- ^ W. C. CAMPBELL; R. W. BURG, , M. H. FISHER, and , R. A. DYBAS (June 26, 1984). "1". The Discovery of Ivermectin and Other Avermectins. American Chemical Society. pp. 5–20. ISBN 9780841210837.
See also[edit]
- Onchocerciasis
- Carter Center
- Lymphatic filariasis
- Neglected diseases
- United Front Against Riverblindness
External links[edit]
- Stromectol
- The Carter Center River Blindness (Onchocerciasis) Control Program
- Mectizan Donation Program
- American NGDO Treating River Blindness
- MERCK. 25 Years: The MECTIZAN® Donation Program
- Trinity College Dublin. Prof William Campbell - The Story of Ivermectin
|
Antiparasitics – Anthelmintics (P02) and Endectocides (QP54)
|
|
| Antiplatyhelmintic agents |
|
Antitrematodals
(schistosomicides)
|
|
Binds tubulin
|
|
|
|
AI
|
|
|
|
Other/unknown
|
- quinoline
- Praziquantel#
- Oxamniquine#
- phenol
- thiazole
- arylsulfonate
|
|
|
|
Anticestodals
(taeniacides)
|
|
Binds tubulin
|
|
|
|
Other/unknown
|
- salicylanilide
- aminoacridine
- butyrophenone
- chlorophenol
|
|
|
|
Antinematodal agents
(including
macrofilaricides) |
|
Binds tubulin
|
- benzimidazole
- Mebendazole#
- Albendazole#
- Thiabendazole
- Fenbendazole
- Ciclobendazole
- Flubendazole
|
|
|
Glutamate-gated chloride channel, GABA receptor
|
- avermectins
- Abamectin
- Doramectin
- Emamectin
- Ivermectin
- Selamectin
- milbemycins
- Moxidectin
- Milbemycin oxime
|
|
|
NMDA
|
- tetrahydropyrimidine
- Pyrantel#
- Pyrantel pamoate
- Oxantel
|
|
|
Other/unknown
|
- piperazine
- Piperazine
- Diethylcarbamazine#
- thiazole
- quinolinium
- benzylammonium
- naphthalenesulfonate
- Tribendimidine
|
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
|
Ectoparasiticides / arthropod (P03A)
|
|
| Insecticide/pediculicide |
|
Chlorine-containing products
|
|
|
|
Chloride channel
|
|
|
|
Organophosphate
|
|
|
|
| Acaricide/miticide/scabicide |
|
Pyrethrines
|
- Permethrin#
- Pyrethrum
- Phenothrin
- Bioallethrin
|
|
|
Chloride channel
|
|
|
|
Sulfur-containing products
|
- Disulfiram
- Dixanthogen
- Mesulfen
- Thiram
|
|
|
Chlorine-containing products
|
|
|
|
Benzoate
|
|
|
|
Organophosphate
|
|
|
|
Other/ungrouped
|
- Dimethicone
- Quassia
- toluidine (Crotamiton)
|
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
