Icaridin
Identification
- Generic Name
- Icaridin
- DrugBank Accession Number
- DB14074
- Background
Icaridin, also known as Picaridin or hydroxy-ethyl isobutyl piperidine carboxylate, is a cyclic amine and a member of the piperidine chemical family. Piperidines are structural components of piperine, which is a plant extract from the genus _Piper _, or pepper. Icaridin has been commonly used as a topically-applied insect repellent in various countries but was officially licensed for use in the United States in 2001 and Canada in 2012 4. Icaridin was synthesized by Bayer in the 1980s based on molecular modeling 4. It is considered to be the first choice of repellent by the Public Health Agency of Canada’s Canadian Advisory Committee on Tropical Medicine and Travel for travelers six months to 12 years of age 1. Icaridin is reported to be less irritating than Diethyltoluamide, another common insect repellant, and products containing up to 20% of icaridin are considered safe for long-term use in adults 3.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 229.3159
Monoisotopic: 229.167793607 - Chemical Formula
- C12H23NO3
- Synonyms
- Icaridin
- Icaridina
- Icaridinum
- Picaridin
- Pikaridin
- Propidine
- External IDs
- EC 423-210-8
- KBR 3023
Pharmacology
- Indication
Icaridin is indicated for use to repel insects, such as mosquitoes, biting flies, ticks, chiggers, and fleas, via topical use or over clothing 5.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prevention of Insect bites ••• ••• •••••••• ••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Icaridin is a cyclic amine and piperidine compound that is expected to stimulate the sensory hairs on the antennae of insects 4.
- Mechanism of action
The exact mechanism and target molecules of icaridin repelling insects are not fully understood; it is presumed that piperine interacts with the olfactory system consisting of odorant receptors (ORs) that need a common co-receptor (ORCO), and of ionotropic receptors (IR) 3, leading to the insect's inability to recognize its host's cues 4. It is also suggested that icaridin may bind to odorant binding protein 1 (AgamOBP1) at different binding sites 2. A study demonstrated that icaridin inhibited the odorant-induced responses of AaOR2 and AaOR8 expressed in Xenopus oocytes, leading to altered olfactory inputs by olfactory sensory neurons (OSN) 3.
Target Actions Organism AOdorant binding protein ligandAnopheles gambiae - Absorption
In a dermal metabolism rat study, dermal application of 20 mg/kg of radio-labeled icaridin resulted in 61-66% of the dose absorbed through the skin 4. Following topical application of 20 mg/kg on rats, the peak plasma concentrations were measured to be 0.5 μg/mL in male rats and 0.8-1.6 μg/mL in female rats 4. In a study of human volunteers, less than 6% of the applied doses were absorbed after topical application of 14.7 or 15.0 mg of technical grade icaridin and covering the application site with a protective wrap for eight hours 4.
- Volume of distribution
In a rat study, dermal application of icaridin at doses of either 20 mg/kg or 200 mg/kg resulted in plasma concentrations ranging from 0.5 μg/ml for males and 0.8-1.6 μg/ml for females in the 20 mg/kg test group, and 4.48 μg/ml in male rats and 1.70 μg/ml and female rats in the 200 mg/kg test group 4. Icaridin applied to the arms of human volunteers was not found in blood plasma 4.
- Protein binding
There is no available information on the protein binding of icaridin.
- Metabolism
There is limited data on the metabolism and resulting metabolites of the drug; however, it is estimated that icaridin undergoes phase I metabolic reactions involving 2-methylpropyl side chain or the piperidine ring being hydroxylated 4. It is also noted that the hydroxyethyl sidechain was oxidized to produce a carbonyl group. There was very little Phase 2 metabolism of the icaridin 4.
- Route of elimination
Following topical administration on rats at doses of 20 mg/kg, urinary excretion was reported to be the primary route of elimination where 73-88% of the parent compound was recovered in the urine 4. At doses of 200 mg/kg, 33-40% of the administered dose was excreted in the urine or feces 4. No data were available on the composition of parent compound and metabolites in the urine of either animals or humans 4.
- Half-life
The first elimination half-lives of icaridin were determined in a study of five male and female rats treated with a single dose of 20 mg/kg icaridin dermally. The half-lives were 35.7 hours for male and 23.9 hours in female rats 6. In another study of rats treated daily for 2 weeks with 20 mg/kg of unlabeled icaridin, followed by exposure to a single dose of 20 mg/kg of the radiolabeled icaridin for 7 days, the 1st elimination half-lives were 10.9 and 9.1 hours for the males and females, respectively 6. The 2nd half-lives were 144 and 105 hours, respectively 6.
- Clearance
There is no available information on the clearance of icaridin.
- Adverse Effects
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- Toxicity
Oral LD50 values in fasted and non-fasted male rats were 2236 mg/kg and 4743 mg/kg, respectively 4. Acute dermal LD50 values in rats were greater than 2000 mg/kg and 5000 mg/kg 4. The LC50 over a 4-hour exposure period exceeded 4364 mg/m^3 in male rats, and the NOEL was determined to be 2153 mg/m^3 4. While icaridin is considered to be practically non-toxic upon dermal and inhalation exposure 4, there have been cases of allergic contact dermatitis associated with pruritis and erythema upon dermal application 6.
In an animal study following application of icaridin to the skin of rats at doses of 50, 100, or 200 mg/kg/day each weekday for two years, there were no signs of potential carcinogenicity 4. The United States Environmental Protection Agency claims that icaridin is not likely to be carcinogenic to humans 6. In a two-generation reproductive study on rats, administering 50, 100, or 200 mg/kg icaridin to the rats' skin weekly beginning 10 weeks before mating and continuing through to weaning of the pups. Findings from the study concluded that chronic icaridin exposure to the skin at doses as high as 200 mg/kg did not result in reproductive toxicity 4.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareOxybenzone Oxybenzone can cause a decrease in the absorption of Icaridin resulting in a reduced serum concentration and potentially a decrease in efficacy. - Food Interactions
- No interactions found.
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.
- International/Other Brands
- Bayrepel / Saltidin
- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image SG Plus Repellent Aroma Mist Liquid 2.1 g/30mL Topical Hankook Samgong Co.,ltd 2017-06-27 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image SG Plus Repellent Aroma Mist Icaridin (2.1 g/30mL) Liquid Topical Hankook Samgong Co.,ltd 2017-06-27 Not applicable US
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Scabies (Sarcoptes scabei) and other insects
Chemical Identifiers
- UNII
- N51GQX0837
- CAS number
- 119515-38-7
- InChI Key
- QLHULAHOXSSASE-UHFFFAOYSA-N
- InChI
- InChI=1S/C12H23NO3/c1-3-10(2)16-12(15)13-8-5-4-6-11(13)7-9-14/h10-11,14H,3-9H2,1-2H3
- IUPAC Name
- butan-2-yl 2-(2-hydroxyethyl)piperidine-1-carboxylate
- SMILES
- CCC(C)OC(=O)N1CCCCC1CCO
References
- General References
- Onyett H: Preventing mosquito and tick bites: A Canadian update. Paediatr Child Health. 2014 Jun;19(6):326-32. [Article]
- Drakou CE, Tsitsanou KE, Potamitis C, Fessas D, Zervou M, Zographos SE: The crystal structure of the AgamOBP1*Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition. Cell Mol Life Sci. 2017 Jan;74(2):319-338. doi: 10.1007/s00018-016-2335-6. Epub 2016 Aug 17. [Article]
- Van Roey K, Sokny M, Denis L, Van den Broeck N, Heng S, Siv S, Sluydts V, Sochantha T, Coosemans M, Durnez L: Field evaluation of picaridin repellents reveals differences in repellent sensitivity between Southeast Asian vectors of malaria and arboviruses. PLoS Negl Trop Dis. 2014 Dec 18;8(12):e3326. doi: 10.1371/journal.pntd.0003326. eCollection 2014 Dec. [Article]
- Gervais, J. A.; Wegner, P.; Luukinen, B.; Buhl, K.; Stone, D. 2009. Picaridin Technical Fact Sheet; National Pesticide Information Center, Oregon State University Extension Services. [Link]
- DailyMed - SG PLUS REPELLENT AROMA MIST- icaridin liquid [Link]
- PICARIDIN - National Library of Medicine HSDB Database - Toxnet - NIH [Link]
- Health Canada Icaridin Evaluation [File]
- External Links
- ChemSpider
- 111359
- 1737729
- ChEBI
- 143733
- ChEMBL
- CHEMBL2104314
- Wikipedia
- Icaridin
- MSDS
- Download (22.5 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Liquid Topical 2.1 g/30mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) < -170 O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1373 boiling point (°C) 208 at 1013 hPa O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1373 water solubility Insoluble Picaridin Technical Fact Sheet; National Pesticide Information Center, Oregon State University Extension Services. - Predicted Properties
Property Value Source Water Solubility 25.1 mg/mL ALOGPS logP 2.19 ALOGPS logP 1.61 Chemaxon logS -0.96 ALOGPS pKa (Strongest Acidic) 15.92 Chemaxon pKa (Strongest Basic) -2.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 49.77 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 62.54 m3·mol-1 Chemaxon Polarizability 26.24 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-1890000000-ec1767cf723d9528250f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-2960000000-70326231b3c75f38060f Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0bw9-3910000000-a4c309b7475d59e88cd3 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-2910000000-dd581d1ac1fb7966d8cf Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0cdl-9600000000-3df5d63a1a6cc3474542 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01ox-9300000000-e5b38bc92409a250a58b Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 155.50142 predictedDeepCCS 1.0 (2019) [M+H]+ 158.47105 predictedDeepCCS 1.0 (2019) [M+Na]+ 167.33298 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Anopheles gambiae
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Not Available
- Specific Function
- Odorant binding
- Gene Name
- OBP-1
- Uniprot ID
- Q8T6S0
- Uniprot Name
- Odorant binding protein
- Molecular Weight
- 16538.985 Da
References
- Drakou CE, Tsitsanou KE, Potamitis C, Fessas D, Zervou M, Zographos SE: The crystal structure of the AgamOBP1*Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition. Cell Mol Life Sci. 2017 Jan;74(2):319-338. doi: 10.1007/s00018-016-2335-6. Epub 2016 Aug 17. [Article]
Drug created at June 16, 2018 23:17 / Updated at February 21, 2021 18:54