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Albendazole
Albendazol · S-oxide · Methyl (6-(propylthio)-1H-benzo[d]imidazol-2-yl)carbamate · ALBEN · ZENTEL · Atasol · ALBENZA · VALBAZEN
Identifikatoren & physikalische Daten
| CAS No. | 54965-21-8 |
|---|---|
| Summenformel | C12H15N3O2S |
| Durchschnittliche Molmasse | 265,33 g/mol |
| Monoisotopische Masse | 265,08849772 g/mol |
| SMILES | CCCSc1ccc2nc(NC(=O)OC)[nH]c2c1 |
| InChIKey | HXHWSAZORRCQMX-UHFFFAOYSA-N |
| PubChem CID | 2082 |
| ChEMBL | CHEMBL1483 |
| ChEBI | CHEBI:16664 |
| EC No. | 259-414-7 |
| DTXSID | DTXSID0022563 |
Chemische & physikalische Eigenschaften
| XLogP | 2,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 92,3 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 5 |
| Schwere Atome | 18 |
| Formalladung | 0 |
| Komplexität | 290 |
| Arzneimittel | PharmaceuticalsPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | log Kow = 1.272.73.24 |
| Color/Form | Colorless crystals |
| Löslichkeit | Practically insoluble2.28e-02 g/L1.4 [ug/mL] (The mean of the results at pH 7.4)Practically insoluble in water, freely soluble in anhydrous formic acid, very slightly soluble in methylene chloride, practically insoluble in ethanol (96 per cent).0.75mg/L(209 ºC) |
| Human Drugs | Breast FeedingLactationMilk, HumanAnti-Infective AgentsAnticestodal AgentsAntiparasitic AgentsAntiprotozoal AgentsFDA approved drugs -> Active ingredientPharmaceuticalsAntifilarials |
| Animal Drugs | Active Ingredients (Albendazole) -> FDA GreenbookPharmaceuticals -> UK Veterinary Medicines Directorate List |
| Schmelzpunkt | 208-210208-210 °CMol wt: 281.34. Active metabolite of albendazole. MP: 226-228 °C (decomposes) /Sulfoxide/209 °C |
| Physical Description | Solid |
| Collision Cross Section | 160.4 Ų [M]+ [CCS Type: DTBuffer gas: N2Ionization: APCI+Dataset: TOXCASTSource Identifier: DTXSID0022563]166.6 Ų [M+H]+ [CCS Type: TWMethod: calibrated with Waters Major Mix]172.57 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]162 Ų [M+H]+ [CCS Type: TW |
| Dichte | 1.2561 (rough estimate) |
| Brechungsindex | 1.6740 (estimate) |
| Lagerbedingungen | 2-8°C |
| pKa (Säurekonstante) | 10.72±0.10(Predicted) |
| Aggregatzustand | Solid |
| Farbe | White to Off-White |
| Merck | 14,210 |
| Henry-Konstante | 1.3×108 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 4 |
| Hauptanwendungen | forensics and toxicologypharmaceutical (small molecule) |
| InChI | InChI=1S/C12H15N3O2S/c1-3-6-18-8-4-5-9-10(7-8)14-11(13-9)15-12(16)17-2/h4-5,7H,3,6H2,1-2H3,(H2,13,14,15,16) |
| InChIKey | HXHWSAZORRCQMX-UHFFFAOYSA-N |
| SMILES | C(OC)(=O)NC1NC2=CC(SCCC)=CC=C2N=1 |
| CAS Datenbank | 54965-21-8(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 3.4% (5 of 149) of reports.DangerH315 (20.1%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P260, P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 149 reports by companies from 22 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Albendazole: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - Carbamic acid, [5-(propylthio)-1H-benzimidazol-2-yl]-, methyl ester: Human health tier I assessment |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl albendazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.Oral dosage form new animal drugs. Albendazole suspension. ... Conditions of use in cattle: Indications for use: Indications for use. For removal and control of the following internal parasites of cattle: Adult liver flukes (Fasciola hepatica)heads and segments of tapeworms (Moniezia benedeni, M. expansa)adult and 4th stage larvae of stomach worms (brown stomach worms including 4th stage inhibited larvae (Ostertagia ostertagi), barberpole worm (Haemonchus contortus, H. placei), small stomach worm (Trichostrongylus axei))adult and 4th stage larvae of intestinal worms (thread-necked intestinal worm (Nematodirus spathiger, N. helvetianus), small intestinal worm (Cooperia punctata and C. oncophora))adult stages of intestinal worms (hookworm (Bunostomum phlebotomum), bankrupt worm (Trichostrongylus colubriformis), nodular worm (Oesophagostomum radiatum))adult and 4th stage larvae of lungworms (Dictyocaulus viviparus). ... Conditions of use in sheep: For removal and control of the following internal parasites of sheep: Adult liver flukes (Fasciola hepatica, Fascioloides magna)heads and segments of common tapeworms (Moniezia expansa) and fringed tapeworm (Thysanosoma actinioides)adult and fourth stage larvae of stomach worms (brown stomach worm (Ostertagia circumcinta and Marshallagia marshalli), barberpole worm (Haemonchus contortus), small stomach worm (Trichostrongylus axei))adult and fourth stage larvae of intestinal worms (thread-necked intestinal worm (Nematodirus spathiger and N. filicollis), Cooper's worm (Cooperia oncophora), bankrupt worm (Trichostrongylus colubriformis), nodular worm (Oesophagostomum columbianum), and large-mouth bowel worm (Chabertia ovina))adult and larval stages of lungworms (Dictyocaulus filaria).Oral dosage form new animal drugs. Albendazole paste. ... Conditions of use in cattle: For removal and control of the following internal parasites of cattle: adult liver flukes (Fasciola hepatica)adult and 4th stage larvae of stomach worms (brown stomach worms including 4th stage inhibited larvae (Ostertagia ostertagi)barberpole worm (Haemonchus contortus, H. placei)small stomach worm (Trichostrongylus axei))adult and 4th stages larvae of intestinal worms (thread-necked intestinal worm (Nematodirus spathiger, N. helvetianus)small intestinal worm (Cooperia punctata and C. oncophora))adult stages of intestinal worms (hookworm (Bunostomum phlebotmum)bankrupt worm (Trichostrongylus colubriformis), nodular worm (Oesophagostomum radiatum))adult and 4th stage larvae of lungworms (Dictyocaulus viviparus).Tolerances - (1) Cattle. A tolerance is established for albendazole 2-aminosulfone (marker residue) in liver (target tissue) of 0.2 part per million and in muscle of 0.05 part per million. (2) Sheep. A tolerance is established for albendazole 2-aminosulfone (marker residue) in liver (target tissue) of 0.25 part per million and in muscle of 0.05 part per million.The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Albendazole is included on this list. |
| Special Reports | Dayan ADPreparing to control Schistosomiasis and Soil-transmitted Helminthiasis in the Twenty-First CenturyActa Tropica 86 (2-3): 141-159 (2003) |
| Hazard Classes and Categories | Skin Irrit. 2 (20.1%) |
| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Allowable Tolerances | Tolerances-(1) Cattle. A tolerance is established for albendazole 2-aminosulfone (marker residue) in liver (target tissue) of 0.2 part per million and in muscle of 0.05 part per million. (2) Sheep. A tolerance is established for albendazole 2-aminosulfone (marker residue) in liver (target tissue) of 0.25 part per million and in muscle of 0.05 part per million. |
| Wechselwirkungen | Regimens in which albendazole with either ivermectin or diethylcarbamazine are given as single annual doses show great promise for controlling lymphatic filariasis occurring either alone or together with other filarial infections. Such combined therapy has the additional benefit of reducing intestinal roundworm infections in school-aged children.... Plasma levels of /albendazole's/ sulfoxide metabolites can be increased by coadministration of glucocorticoids and possibly praziquantel. |
| Hepatotoxicity | Albendazole therapy has been associated with transient and asymptomatic elevations in serum aminotransferase levels in up to 50% of patients treated for more than a few weeks. These abnormalities rapidly improve with stopping therapy which is rarely required (~4%). Albendazole has also been associated with rare instances of clinically apparent liver injury. The onset of injury has been within a few days to as long as 2 months of starting therapy or more rapidly with multiple courses of treatment. The injury can also arise 1 to 2 weeks after a short course of albendazole (1 to 3 days). The pattern of serum enzyme elevations is typically hepatocellular or mixed. Allergic features (rash, fever, eosinophilia) may be present but are not prominent. Most cases have been mild to moderate in severity, and recovery is distinctively rapid once the drug is stopped. However, severe and even fatal cases of albendazole induced liver injury have been reported. Rapid recurrence with rechallenge has been reported but with similar severity. Cases with acute liver failure leading to emergency liver transplantation or death have also occurred. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a log Kow of 1.27(2) and a regression-derived equation(3), indicates that albendazole is expected to have high mobility in soil(SRC). Volatilization of albendazole from moist soil surfaces is not expected to be an important fate process(SRC) based on an estimated Henry's Law constant of the neutral species is 7.6X10-14 atm-cu m/mole(SRC), determined using a fragment constant estimation method(4). Albendazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.5X10-9 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2006).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a log Kow of 1.27(2) and a regression-derived equation(3), indicates that albendazole is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.6X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 5(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Based on an estimated rate constant of 2.6X10-4 L/mole-sec(7), half-lives for the hydrolysis of albendazole at pH 7 and 8 are 840 and 84 years, respectively. Measured half-lives for the direct photolysis of albendazole in sunlit water at pH 5,7, and 9 are 10, 16, and 6 minutes, respectively, under summer conditions and 50, 80, and 20 minutes, respectively, under winter conditions(8,9). Biodegradation data were not available(SRC, 2006).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), albendazole, which has an estimated vapor pressure of 1.5X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase albendazole may be removed from the air by wet or dry deposition(SRC). Albendazole is expected to undergo direct photolysis based on measured half-lives in sunlit waters at pH 5, 7, and 9 of 10, 16, and 6 minutes, respectively, under summer conditions and 50, 80, and 20 minutes, respectively, under winter conditions(3,4). |
| Unerwünschte Wirkungen | The most common adverse effects accompanying albendazole use are headaches and elevated liver enzymes, with 10% to 20% of patients experiencing elevated liver enzymes. Some other side effects of albendazole include abdominal pain, nausea, vomiting, and fever. A small percentage of patients may experience a hypersensitivity reaction to the drug, such as hives and pruritus. There are reports of alopecia and telogen effluvium in the literature as rare side effects of albendazole therapy. Fortunately, alopecia and telogen effluvium usually reverse after completing the treatment. |
| Expositionspfade | Poorly absorbed from the gastrointestinal tract due to its low aqueous solubility. Oral bioavailability appears to be enhanced when coadministered with a fatty meal (estimated fat content 40 g) |
| Toxizitätsübersicht | Albendazole's low solubility prevents it from being absorbed in large enough quantities to be toxic to humans. There is no specific antidote for albendazole overdose.Albendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Due to diminished energy production, the parasite is immobilized and eventually dies. |
| Signs and Symptoms | Symptoms of overdose include elevated liver enzymes, headaches, hair loss, low levels of white blood cells (neutropenia), fever, and itching. |
| Soil Adsorption/Mobility | The Koc of albendazole is estimated as 120(SRC), using a log Kow of 1.27(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that albendazole is expected to have high mobility in soil. |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ ... Adverse effects include fever, reversible leucopenia, headache, nausea, dizziness, sleeplessness, epigastric pain and diarrhoea./CASE REPORTS/ Albendazole is a benzimidazole with wide spectrum coverage as an antiparasitic drug. Reported side effects have been minimal. ... The case of a patient who died with severe prolonged pancytopenia beginning during the third week of therapy for a pulmonary echinococcal cyst /is reported/. This case was a 68-year-old man who presented with a large cystic lung mass. His medical history was significant for Child-Pugh class B cirrhosis. A prolonged course of albendazole was initiated. Two weeks later, the patient presented in septic shock with severe pancytopenia. The patient was initially resuscitated, but died after 10 days with no marrow recovery. Autopsy was consistent with albendazole-induced pancytopenia. This is the third human case of pancytopenia and the first death reported in relation to albendazole-induced pancytopenia. Neutropenia seems to be related more to higher dosage and longer duration of use. Albendazole sulfoxide peak dose and half life are significantly prolonged by liver disease and concomitant administration of certain drugs. The severity and duration of albendazole-induced pancytopenia in this case was likely related to the underlying liver disease. Frequent serial monitoring of blood counts and cessation of medication with any evidence of marrow toxicity in such patients is warranted./OTHER TOXICITY INFORMATION/ Albendazole at 10 to 12 mg/kg/day has been given continuously for 3 to 6 mo without producing serious or irreversible toxicity. |
| Artificial Pollution Sources | Albendazole's production and use as an anthelmintic drug in humans and animals(1,2) may result in its release to the environment through various waste streams(SRC). |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)AlbendazolevMost-DILI-concern7Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015 |
| Wassergefährdungsklasse (WGK) | 2 |
| Zollcode | 29332990 |
| RTECS-Nr. | FD1100000 |
| R-Sätze (R) | 61-36/37/38-48/22-63-33 |
| Gefahrensymbole | T,Xn |
| Sicherheitshinweise (S) | 53-45-37/39-26-36/37-24/25 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 54965-21-8(Hazardous Substances Data) |
| Gefahrenklasse | Aquatic Acute 1Aquatic Chronic 1Repr. 2STOT RE 2 Oral |
Anwendungen & Verwendung
Verwenden
Albendazole is a derivative of benzimidazole, is a drug with a broad antihelmintic spectrum. It exhibits an antihelmintic effect against sensitive cestodes and nematodes by blocking the process of glucose uptake by the parasites, which is expressed in the depletion of glycogen reserves and subsequent reduction in the level of adenosintriphophate. As a result, the parasite stops moving and dies. It is used upon infection of Acaris lumbricoides, Ancylostoma duodenale, Necator americanus, Enterobius vermicularis, and Trichuris trichiura. Synonyms of this drug are SKF 62979 and others.