Ivermectin
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Overview
- Description
- A medication used to treat a number of worm infections as well as head lice.
- Description
- A medication used to treat a number of worm infections as well as head lice.
- DrugBank ID
- DB00602
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 3
- Phase 1
- 35
- Phase 2
- 79
- Phase 3
- 85
- Phase 4
- 23
Identification
- Summary
Ivermectin is an anti parasite medication used to treat head lice, onchocerciasis, strongyloidiasis, ascariasis, trichuriasis, and enterobiasis.
- Brand Names
- Sklice, Soolantra, Stromectol
- Generic Name
- Ivermectin
- DrugBank Accession Number
- DB00602
- Background
Ivermectin is a semi-synthetic antiparasitic medication derived from avermectins, a class of highly-active broad-spectrum antiparasitic agents isolated from the fermentation products of Streptomyces avermitilis.8 Ivermectin itself is a mixture of two avermectins, comprising roughly 90% 5-O-demethyl-22,23-dihydroavermectin A1a (22,23-dihydroavermectin B1a) and 10% 5-O-demethyl-25-de(1-methylpropyl)-22,23-dihydro-25-(1-methylethyl)avermectin A1a (22,23-dihydroavermectin B1b).8
Ivermectin is mainly used in humans in the treatment of onchocerciasis, but may also be effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis). Applied topically, it may be used in the treatment of head lice infestation.
With the advent of 2020 and the COVID-19 pandemic, ivermectin began garnering notoriety due to its off-label use for the prophylaxis and treatment of COVID-19. While studies are still ongoing, much of the evidence for ivermectin in COVID-19 relies on pre-print in vitro data, and the clinical utility of this data remains unclear. Due to a number of factors - for example, the relatively low number of patients per trial and the speed at which these trials were conducted - studies on the use of ivermectin in COVID-19 have been fraught with statistical errors and accusations of plagiarism.9,5 In addition, the use of aggregate patient data in large-scale meta-analyses (as opposed to individual patient data (IPD)) has been shown to disguise otherwise blatant data errors, such as extreme terminal digit bias and the duplication of blocks of patient records.5
Until high-quality, peer-reviewed data regarding both the safety and efficacy of ivermectin for COVID-19 in humans becomes available, the use of ivermectin for these purposes should be avoided in favour of thoroughly-vetted therapies (e.g. COVID-19 vaccines like Comirnaty).
- Type
- Small Molecule
- Groups
- Approved, Investigational, Vet approved
- Structure
- Weight
- Average: 1736.185
Monoisotopic: 1735.000064061 - Chemical Formula
- C95H146O28
- Synonyms
- Ivermectin
- Ivermectina
- Ivermectine
- Ivermectinum
- External IDs
- L 640471
- L-640471
- MK 933
- MK-0933
- MK-933
Pharmacology
- Indication
Administered topically, ivermectin cream is indicated for the treatment of inflammatory lesions associated with rosacea.7 An over-the-counter ivermection lotion is commercially available and indicated for the topical treatment of head lice infestations in patients ≥6 months of age.6
Orally administered ivermectin is indicated as a broad-spectrum anti-parasitic for the treatment of intestinal strongyloidiasis caused by Strongyloides stercoralis and onchocerciasis caused by Onchocerca volvulus.8 Systemic ivermectin therapy is used internationally for the treatment of various tropical diseases, including filariasis, cutaneous larva migrans, and Loa loa infection, amongst others.2
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Ascariasis ••• ••••• Treatment of Demodex infestation ••• ••••• Treatment of Enterobiasis ••• ••••• Treatment of Filariasis caused by loa loa ••• ••••• Treatment of Gnathostomiasis ••• ••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Ivermectin is a semisynthetic, anthelminitic agent. It is an avermectin, a group of pentacyclic sixteen-membered lactones (i.e. a macrocyclic lactone disaccharide) derived from the soil bacterium Streptomyces avermitilis. Avermectins are potent and broad-spectrum anti-parasitic agents.
- Mechanism of action
Ivermectin 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.
- Absorption
Moderately 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 binding
93%
- 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.
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- Route of elimination
Ivermectin 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-life
Following oral administration, the half-life of ivermectin is approximately 18 hours.8
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Used appropriately, topically applied ivermectin lotions and creams are unlikely to cause significant toxicity. With accidental or intentional significant exposure to unknown quantities of veterinary formulations of ivermectin (by ingestion, inhalation, injection, or significant body surface area exposure) patients have reported rash, edema, headache, dizziness, asthenia, nausea, vomiting, and diarrhea. Other less common effects include seizure, ataxia, dyspnea, abdominal pain, paresthesia, urticaria, and contact dermatitis.8 Overdosage with orally administered ivermectin was lethal in mice and rats (at doses several-fold higher than the recommended dose), with death preceded by significant ataxia, bradypnea, tremors, ptosis, decreased activity, emesis, and mydriasis.8
If overdosage of ivermectin is suspected, initiate supportive therapy as clinically indicated, including the use of parenteral fluids and electrolytes, respiratory support, and pressor agents to manage hypotension. Induction of emesis and/or gastric lavage may be considered alongside other purgatives and routine anti-poison measures if clinically indicated.8
- 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 softwareAbametapir The serum concentration of Ivermectin can be increased when it is combined with Abametapir. Abemaciclib Abemaciclib may decrease the excretion rate of Ivermectin which could result in a higher serum level. Acenocoumarol Ivermectin may increase the anticoagulant activities of Acenocoumarol. Acipimox The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Ivermectin is combined with Acipimox. Afatinib Afatinib may decrease the excretion rate of Ivermectin which could result in a higher serum level. - Food Interactions
- Take on an empty stomach. Oral ivermectin should be taken on an empty stomach with a glass of water.
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.
- Product Images
- International/Other Brands
- Ascapil (Abbott) / Detebencil (Roux-Ocefa) / Ermetin (Unipharm) / Gotax (Metlen) / Imectin (Pulse) / Ivectin (Aristopharma) / Ivera (Beximco) / Ivergot (Licol) / Ivermec (UCI) / Ivexterm (Valeant) / Ivori (Invision) / Kaonol (Mediderm) / Kilox (Bussié) / Maikeding (Hisun) / Quanox (Dermacare) / Revectina (Solvay) / Scabo (Delta) / Scavista (Zuventus) / Securo (Valeant) / Vermectin (Atlantic Lab)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rosiver Cream 1 % w/w Topical Galderma Italia S.P.A. 2015-05-25 Not applicable Canada Sklice Lotion 5 mg/1g Topical Arbor Pharmaceuticals 2016-06-30 Not applicable US Sklice Lotion 0.585 g/117g Topical Sanofi Pasteur Inc. 2012-07-09 2017-07-31 US Soolantra Cream 10 mg/1g Topical Galderma Laboratories, L.P. 2015-01-01 Not applicable US Stromectol Tablet 3 mg Oral Merck Ltd. 2018-11-06 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ivermectin Cream 10 mg/1g Topical Padagis US LLC 2021-06-07 Not applicable US Ivermectin Tablet 3 mg/1 Oral bryant ranch prepack 2014-11-15 Not applicable US Ivermectin Cream 10 mg/1g Topical Prasco Laboratories 2019-10-15 2022-10-15 US Ivermectin Cream 10 mg/1g Topical Padagis Israel Pharmaceuticals Ltd 2024-01-08 Not applicable US Ivermectin Cream 10 mg/1g Topical Zydus Lifesciences Limited 2023-06-10 Not applicable US - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ivermectin Lotion 5 mg/1g Topical Belmora LLC 2024-08-12 Not applicable US Ivermectin Lotion 5 mg/1g Topical Taro Pharmaceuticals U.S.A., Inc. 2020-05-06 Not applicable US Ivermectin Lotion 5 mg/1g Topical Rite Aid Corporation 2020-05-06 Not applicable US Ivermectin Lotion 5 mg/1g Topical Walgreen Company 2020-05-06 Not applicable US Ivermectin Lotion 5 mg/1g Topical CVS PHARMACY 2020-05-06 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 171083 Ivermectin 1% / Metronidazole 1% / Niacinamide 4% Ivermectin (1 g/100g) + Metronidazole (1 g/100g) + Nicotinamide (4 g/100g) Gel Topical Sincerus Florida, LLC 2020-07-02 Not applicable US Brimonidine Tartrate 0.25% / Ivermectin 1% / Metronidazole 1% / Niacinamide 4% Ivermectin (1 g/100g) + Brimonidine tartrate (0.25 g/100g) + Metronidazole (1 g/100g) + Nicotinamide (4 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-16 Not applicable US Ivermectin 1% / Metronidazole 1% Ivermectin (1 g/100g) + Metronidazole (1 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-01 Not applicable US Ivermectin 1% / Metronidazole 1% / Niacinamide 4% Ivermectin (1 g/100g) + Metronidazole (1 g/100g) + Nicotinamide (4 g/100g) Gel Topical Sincerus Florida, LLC 2019-05-01 Not applicable US Neck Hump Removal Patch Ivermectin (14 g/1001) Patch Topical Guangzhou Hanhai Trading Co., Ltd 2023-09-19 Not applicable US
Categories
- ATC Codes
- P02CF01 — Ivermectin
- P02CF — Avermectines
- P02C — ANTINEMATODAL AGENTS
- P02 — ANTHELMINTICS
- P — ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
- Drug Categories
- Agents Causing Muscle Toxicity
- Agrochemicals
- Anthelmintics
- Anti-Infective Agents
- Antinematodal Agents
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Avermectines
- BCRP/ABCG2 Substrates
- Compounds used in a research, industrial, or household setting
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Dermatologicals
- Insecticides
- Lactones
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Pediculicides
- Pesticides
- Polyketides
- Scabicides and Pediculicides
- Toxic Actions
- Classification
- Not classified
- Affected organisms
- Parasitic nematodes and other roundworms
- Head lice
Chemical Identifiers
- UNII
- 8883YP2R6D
- CAS number
- 70288-86-7
- InChI Key
- SPBDXSGPUHCETR-JFUDTMANSA-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+/m00/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[15.6.1.1^{4,8}.0^{20,24}]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-[(2S)-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[15.6.1.1^{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@H](O[C@H]4C[C@H](OC)[C@@H](O[C@H]5C[C@H](OC)[C@@H](O)[C@H](C)O5)[C@H](C)O4)\C(C)=C\C[C@]4([H])C[C@@]([H])(C[C@]5(CC[C@H](C)[C@]([H])(O5)C(C)C)O4)OC(=O)[C@]([H])(C=C(C)[C@H]1O)[C@@]23O.[H][C@@]12OC\C3=C/C=C/[C@H](C)[C@H](O[C@H]4C[C@H](OC)[C@@H](O[C@H]5C[C@H](OC)[C@@H](O)[C@H](C)O5)[C@H](C)O4)\C(C)=C\C[C@]4([H])C[C@@]([H])(C[C@]5(CC[C@H](C)[C@]([H])(O5)[C@@H](C)CC)O4)OC(=O)[C@]([H])(C=C(C)[C@H]1O)[C@@]23O
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 References
- El-Saber Batiha G, Alqahtani A, Ilesanmi OB, Saati AA, El-Mleeh A, Hetta HF, Magdy Beshbishy A: Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects. Pharmaceuticals (Basel). 2020 Aug 17;13(8). pii: ph13080196. doi: 10.3390/ph13080196. [Article]
- Mathachan SR, Sardana K, Khurana A: Current Use of Ivermectin in Dermatology, Tropical Medicine, and COVID-19: An Update on Pharmacology, Uses, Proven and Varied Proposed Mechanistic Action. Indian Dermatol Online J. 2021 Jul 14;12(4):500-514. doi: 10.4103/idoj.idoj_298_21. eCollection 2021 Jul-Aug. [Article]
- Alam S, Kamal TB, Sarker MMR, Zhou JR, Rahman SMA, Mohamed IN: Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021. Front Pharmacol. 2021 Jun 14;12:659577. doi: 10.3389/fphar.2021.659577. eCollection 2021. [Article]
- Bestetti RB, Furlan-Daniel R, Silva VMR: Pharmacological Treatment of Patients with Mild to Moderate COVID-19: A Comprehensive Review. Int J Environ Res Public Health. 2021 Jul 5;18(13). pii: ijerph18137212. doi: 10.3390/ijerph18137212. [Article]
- Lawrence JM, Meyerowitz-Katz G, Heathers JAJ, et al.: The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable. Nat Med. [Article]
- FDA Approved Drug Products: Sklice (ivermectin 0.5%) topical lotion (OTC) [Link]
- FDA Approved Drug Products: Soolantra (ivermectin 1%) topical cream [Link]
- FDA Approved Drug Products: Stromectol (Ivermectin) Oral Tablet [Link]
- Nature News: Flawed ivermectin preprint highlights challenges of COVID drug studies [Link]
- CDC Health Alert Network: Rapid Increase in Ivermectin Prescriptions and Reports of Severe Illness Associated with Use of Products Containing Ivermectin to Prevent or Treat COVID-19 [Link]
- External Links
- Human Metabolome Database
- HMDB0014740
- KEGG Drug
- D00804
- KEGG Compound
- C07970
- PubChem Compound
- 46936176
- PubChem Substance
- 46506810
- ChemSpider
- 7988461
- 6069
- ChEMBL
- CHEMBL1200633
- Therapeutic Targets Database
- DAP000261
- PharmGKB
- PA450133
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ivermectin
- FDA label
- Download (60.2 KB)
- MSDS
- Download (73.4 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Helminthiasis / Intestinal Worms 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Basic Science Helminth Infection / Malnutrition / Tuberculosis (TB) 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) 3 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / Hydroxychloroquine / Ivermectin 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / Severe Acute Respiratory Syndrome (SARS) / Ventilation Pneumonitis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Merck and co inc
- Packagers
- Gallipot
- Merck & Co.
- Dosage Forms
Form Route Strength Injection Subcutaneous Solution Subcutaneous Granule Oral Paste Oral Tablet Oral 3.00 mg Tablet, chewable Oral Tablet, chewable Oral Liquid Topical Injection Parenteral Solution Oral Suspension Oral 6 mg Injection, solution Subcutaneous Tablet Oral 12 Mg Cream Topical 10 mg/1g Powder Not applicable 1 kg/1kg Gel Topical Solution Oral 6 mg Tablet Oral 6.000 mg Powder Oral Solution Oral 600000 mg Capsule, liquid filled Oral 3 mg Capsule, liquid filled Oral 300000 mg Solution Oral 0.6 g Patch Topical 14 g/1001 Solution Oral 600 mg Cream Oral 10.000 mg Suspension Oral Solution Topical 0.1 g Cream Topical 1 % w/w Tablet Oral Solution Oral 0.006 g Lotion Topical 0.585 g/117g Lotion Topical 5 mg/1g Cream 10 mg/g Cream Topical 10 mg/g Cream Topical 1 g Tablet Oral 3 mg/1 Tablet Oral 6 mg/1 Tablet Oral 3 mg Solution Topical Tablet Oral 6 mg Tablet, film coated 6 mg - Prices
Unit description Cost Unit Stromectol 20 3 mg tablet Box 116.13USD box Ivermectin powder 14.0USD g Stromectol 3 mg tablet 5.58USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8927595 No 2015-01-06 2027-10-12 US US8791153 No 2014-07-29 2027-10-12 US US6103248 No 2000-08-15 2018-05-22 US US9089587 No 2015-07-28 2034-03-13 US US8470788 No 2013-06-25 2024-04-22 US US9233118 No 2016-01-12 2034-03-13 US US9233117 No 2016-01-12 2034-03-13 US US7550440 No 2009-06-23 2024-04-22 US US8815816 No 2014-08-26 2024-04-22 US US8093219 No 2012-01-10 2024-04-22 US US8080530 No 2011-12-20 2024-04-22 US US6133310 No 2000-10-17 2019-04-26 US US5952372 No 1999-09-14 2018-09-18 US US8415311 No 2013-04-09 2024-04-22 US US9782425 No 2017-10-10 2034-03-13 US US10206939 No 2019-02-19 2034-03-13 US US11033565 No 2021-06-15 2024-04-22 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 155 °C Not Available water solubility Insoluble Not Available - Predicted Properties
Property Value Source Water Solubility 0.00614 mg/mL ALOGPS logP 4.37 ALOGPS logP 5.83 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 12.47 Chemaxon pKa (Strongest Basic) -3.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 13 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 170.06 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 230.33 m3·mol-1 Chemaxon Polarizability 95.55 Å3 Chemaxon Number of Rings 14 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8146 Blood Brain Barrier - 0.549 Caco-2 permeable - 0.8192 P-glycoprotein substrate Substrate 0.8771 P-glycoprotein inhibitor I Inhibitor 0.805 P-glycoprotein inhibitor II Inhibitor 0.8192 Renal organic cation transporter Non-inhibitor 0.7384 CYP450 2C9 substrate Non-substrate 0.8877 CYP450 2D6 substrate Non-substrate 0.886 CYP450 3A4 substrate Substrate 0.7714 CYP450 1A2 substrate Non-inhibitor 0.9129 CYP450 2C9 inhibitor Non-inhibitor 0.8366 CYP450 2D6 inhibitor Non-inhibitor 0.928 CYP450 2C19 inhibitor Non-inhibitor 0.8793 CYP450 3A4 inhibitor Non-inhibitor 0.7957 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8073 Ames test Non AMES toxic 0.8295 Carcinogenicity Non-carcinogens 0.9622 Biodegradation Not ready biodegradable 0.9759 Rat acute toxicity 3.5285 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9471 hERG inhibition (predictor II) Non-inhibitor 0.5536
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Zeng Z, Andrew NW, Arison BH, Luffer-Atlas D, Wang RW: Identification of cytochrome P4503A4 as the major enzyme responsible for the metabolism of ivermectin by human liver microsomes. Xenobiotica. 1998 Mar;28(3):313-21. doi: 10.1080/004982598239597 . [Article]
- Kudzi W, Dodoo AN, Mills JJ: Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans? BMC Med Genet. 2010 Jul 14;11:111. doi: 10.1186/1471-2350-11-111. [Article]
- Juarez M, Schcolnik-Cabrera A, Duenas-Gonzalez A: The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018 Feb 1;8(2):317-331. eCollection 2018. [Article]
- Skalova L, Szotakova B, Machala M, Neca J, Soucek P, Havlasova J, Wsol V, Kridova L, Kvasnickova E, Lamka J: Effect of ivermectin on activities of cytochrome P450 isoenzymes in mouflon (Ovis musimon) and fallow deer (Dama dama). Chem Biol Interact. 2001 Aug 31;137(2):155-67. doi: 10.1016/s0009-2797(01)00227-7. [Article]
- FDA Approved Drug Products: Stromectol (Ivermectin) Oral Tablet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Have shown involvement in the in vitro metabolism of ivermectin, but are likely minor contributors (if at all).
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: Stromectol (Ivermectin) Oral Tablet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Have shown involvement in the in vitro metabolism of ivermectin, but are likely minor contributors (if at all).
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- FDA Approved Drug Products: Stromectol (Ivermectin) Oral Tablet [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Menez C, Mselli-Lakhal L, Foucaud-Vignault M, Balaguer P, Alvinerie M, Lespine A: Ivermectin induces P-glycoprotein expression and function through mRNA stabilization in murine hepatocyte cell line. Biochem Pharmacol. 2012 Jan 15;83(2):269-78. doi: 10.1016/j.bcp.2011.10.010. Epub 2011 Oct 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- ABC-type glutathione S-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 06, 2024 19:36