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Albendazole (formerly SKF-62979; SKF62979; SKF 62979; Zentel; Albenza; Eskazole; Valbazen), a benzimidazole analog and tubulin inhibitor, is an orally bioavailable anti-parasitic drug that has been approved for use in the treatment of various worm infestations such as giardiasis, neurocysticercosis, filariasis, hydatid disease, trichuriasis, pinworm disease, and ascariasis, among others. It acts as a tubulin inhibitor that binds to the colchicine-sensitive site of β-tubulin, thus inhibiting its polymerization or assembly into microtubules.
Physicochemical Properties
| Molecular Formula | C12H15N3O2S | |
| Molecular Weight | 265.33 | |
| Exact Mass | 265.088 | |
| CAS # | 54965-21-8 | |
| Related CAS # | Albendazole sulfoxide;54029-12-8;Albendazole sulfoxide-d3;1448346-38-0;Albendazole-d3;1353867-92-1;Albendazole-d7;1287076-43-0 | |
| PubChem CID | 2082 | |
| Appearance | White to off-white solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Melting Point | 207-211°C（分解） | |
| Index of Refraction | 1.634 | |
| LogP | 3.07 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 18 | |
| Complexity | 291 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | HXHWSAZORRCQMX-UHFFFAOYSA-N | |
| InChi Code | 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) | |
| Chemical Name | methyl N-(6-propylsulfanyl-1H-benzimidazol-2-yl)carbamate | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | In a dose-dependent manner, albendazole (100, 500, 1000 nM; 1, 3, or 5 days) inhibits the proliferation of cells[1]. SKHEP-1 cells are arrested by albendazole (100, 250, 500, 1000 nM; 3 days) at both the G0-G1 (250, 500 nM) and G2-M (1000 nM) phases of the cycle[1]. Albendazole (5 μM; 24, 36 h) primarily causes late apoptosis in HCT-1 16, HT29, and SW480 cells, along with time-dependent PARP and caspase-3 cleavage[2]. It also primarily causes early apoptosis in HCT-15 cells. In HCT-15, HCT-1 16, HT29, and SW480 cells, benendazole (5 μM; 24, 36 h) induces autophagy by upregulating the expression level of autophagy-related proteins (LC3, Atg7, p-beclin-1, and beclin-1)[2]. In A549 cells, albendazole (500 nM, 24 h) suppresses the expression of VEGF and HIF-1α induced by hypoxia[3]. |
| ln Vivo | In mice, albendazole (10 mg/kg; ir; once daily for 30 days) decreases the weight of Echinococcus granulosus cysts[4]. ?For 20 days, albendazole (300 mg/kg; po; daily in two divided doses) significantly inhibits the formation of tumors in vivo[1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: SKHEP-1 cells Tested Concentrations: 100, 500, 1000 nM Incubation Duration: 1, 3, or 5 days Experimental Results: Inhibited cell proliferation in a dose-dependent manner. Cell Cycle Analysis[1] Cell Types: SKHEP-1 HCC cells Tested Concentrations: 100, 250, 500, 1000 nM Incubation Duration: 3 days Experimental Results: demonstrated dose-dependent effect on the cell cycle kinetics. Apoptosis Analysis[2] Cell Types: HCT-15, HCT-1 16, HT29, SW480 cells Tested Concentrations: 5 µM Incubation Duration: 24, 36 h Experimental Results: Promoted apoptosis in colon cancer cells. Cell Autophagy Assay[2] Cell Types: HCT -15, HCT-1 16, HT29, SW480 cells Tested Concentrations: 5 µM Incubation Duration: 24, 36 h Experimental Results: Induced autophagy in colon cancer cells. Western Blot Analysis[2] Cell Types: HCT-15, HCT-1 16, HT29, SW480 cells Tested Concentrations: 5 µM Incubation Duration: 12, 24, 36 h Experimental Results: Induced apoptosis-related protein (PARP, caspase-3) and autophagy-related protein (such as LC3, Atg7, p-beclin-1, and beclin-1) expression level in a time-dependent manner. In |
| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse (10-week-age; Echinococcus granulosus infection model)[4]. Doses: 10 mg/kg Route of Administration: po (oral gavage); one time/day for 30 days. Experimental Results: decreased Echinococcus granulosus cyst weights. Animal/Disease Models: Male BALB/c Nu/nu (nude) mice (6 to 10weeks old; inoculated subcutaneously (sc) with SKHEP-1)[1]. Doses: 50, 150, 300 mg/kg Route of Administration: Oral administration; per day in two divided dose for 20 days. Experimental Results: Profoundly suppressed tumor growth in vivo. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion 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) Albendazole is rapidly converted in the liver to the primary metabolite, albendazole sulfoxide, which is further metabolized to albendazole sulfone and other primary oxidative metabolites that have been identified in human urine. Urinary excretion of albendazole sulfoxide is a minor elimination pathway with less than 1% of the dose recovered in the urine. Biliary elimination presumably accounts for a portion of the elimination as evidenced by biliary concentrations of albendazole sulfoxide similar to those achieved in plasma. Albendazole is variably and erractically absorbed after oral admin; absorption is enhanced by the presence of fatty foods and possibly by bile salts as well. After a 400-mg oral dose, albendazole cannot be detected in plasma, because the drug is rapidly metabolized in the liver and possibly in the intestine as well, to albendazole sulfoxide, which has potent anthelmintic activity. Both the (+) and (-) enantiomers of albendazole sulfoxide are formed, but in human beings the (+) enantiomer reaches much higher peak concn in plasma and is cleared much more slowly than the (-) form. Total sulfoxide attains peak plasma concn of about 300 ng/mL, but with wide interindividual variation. Albendazole sulfoxide is about 70% bound to plasma proteins ... It is well distributed into various tissues, including hydatid cysts, where it reaches a concn of about one-fifth that in plasma ... Both sulfoxide derivatives are oxidized further to the nonchiral sulfone metabolite of albendazole, which is pharmacologically inactive; this reaction favors the (-) sulfoxide and probably becomes rate limiting in determining the clearance ... Albendazole metabolites are excreted mainly in the urine. Oral bioavailability of albendazole appears to be increased when the drug is administered with a fatty meal; when the drug is administered with meals containing about 40 g of fat, plasma concentrations of albendazole sulfoxide are up to 5 times higher than those observed when the drug is administered to fasting patients Sheep bearing permanent ruminal and abomasal cannulae were given a single oral dose of 10 mg/kg bw albendazole as a 2.5% formulation. Albendazole was absorbed unchanged from the rumen. Once in the body it was rapidly degraded, and sulfone metabolites were detected in plasma, the former achieving the greater level. All 3 compounds were present in the abomasum. Presumably albendazole was passed through the stomachs while the metabolites were secreted or diffused into this organ. Non-detectable levels of all 3 compounds were reached in plasma and rumen at 96 hr and in abomasum at 120 hr. The parent compound was virtually undetectable in the plasma of Sprague Dawley males and females given a single gavage dose of 10.6 mg/kg bw albendazole in an aqueous suspension. Rapid metabolism let to the appearance of the sulfoxide and subsequently the sulfone derivatives in plasma. Both metabolites decreased to very low levels at 18 hr. Daily dosing at 10.6 mg/kg bw in males for a period of 10 days resulted in lower plasma levels of sulfoxide and higher levels of the sulfone. Albendazole induces certain hepatic drug-metabolising enzymes, which may be responsible for enhancing the degradation of sulfoxide to sulfone following repeated administration. For more Absorption, Distribution and Excretion (Complete) data for ALBENDAZOLE (9 total), please visit the HSDB record page. Metabolism / Metabolites Hepatic. Rapidly converted in the liver to the primary metabolite, albendazole sulfoxide, which is further metabolized to albendazole sulfone and other primary oxidative metabolites that have been identified in human urine. Albendazole is converted first to a sulfoxide and then to a sulfone. All of these reactions are catalyzed by flavin monooxygenases (FMO) and/or cytochrome P450. Both enzymes are efficient catalysts of S-oxygenation ... Albendazole is metabolized in the liver to an active metabolite, albendazole sulfoxide, which accounts for detectable plasma concentrations of the drug; systemic anthelmintic activity of the drug has been attributed to this metabolite. Albendazole ... is rapidly metabolized in the liver and possibly in the intestine as well, to albendazole sulfoxide, which has potent anthelmintic activity. Both the (+) and (-) enantiomers of albendazole sulfoxide are formed, but in human beings the (+) enantiomer reaches much higher peak concn in plasma and is cleared much more slowly than the (-) form. Total sulfoxide attains peak plasma concn of about 300 ng/mL, but with wide interindividual variation. Albendazole sulfoxide is about 70% bound to plasma proteins and has a highly variable plasma half-life ranging from about 4 to 15 hr. It is well distributed into various tissues, including hydatid cysts, where it reaches a concn of about one-fifth that in plasma. This probably explains why albendazole is more effective than mebendazole for treating hydatid cyst disease. Formation of albendazole sulfoxide is catalyzed by both microsomal flavin monooxygenase and isoforms of cytochrome P450 in the liver and possibly also in the intestine. Hepatic flavin monooxygenase activity appears associated with (+) albendazole sulfoxide formation, whereas cytochromes P450 preferentially produce the (-) sulfoxide metabolite. Both sulfoxide derivatives are oxidized further to the nonchiral sulfone metabolite of albendazole, which is pharmacologically inactive; this reaction favors the (-) sulfoxide and probably becomes rate limiting in determining the clearance and plasma half-life of the bioactive (+) sulfoxide metabolite. Induction of enzymes involved in sulfone formation from the (+) sulfoxide could account for some of the wide variation noted in plasma half-lives of albendazole sulfoxide. Indeed, in animal models, benzimidazoles can induce their own metabolism. Albendazole metabolites are excreted mainly in the urine. Sheep bearing permanent ruminal and abomasal cannulae were given a single oral dose of 10 mg/kg bw albendazole as a 2.5% formulation. Albendazole was absorbed unchanged from the rumen. Once in the body it was rapidly degraded, and sulfone metabolites were detected in plasma, the former achieving the greater level. All 3 compounds were present in the abomasum. Presumably albendazole was passed through the stomachs while the metabolites were secreted or diffused into this organ. Non-detectable levels of all 3 compounds were reached in plasma and rumen at 96 hr and in abomasum at 120 hr. For more Metabolism/Metabolites (Complete) data for ALBENDAZOLE (12 total), please visit the HSDB record page. Albendazole has known human metabolites that include Albendazole oxide. Hepatic. Rapidly converted in the liver to the primary metabolite, albendazole sulfoxide, which is further metabolized to albendazole sulfone and other primary oxidative metabolites that have been identified in human urine. Route of Elimination: Albendazole is rapidly converted in the liver to the primary metabolite, albendazole sulfoxide, which is further metabolized to albendazole sulfone and other primary oxidative metabolites that have been identified in human urine. Urinary excretion of albendazole sulfoxide is a minor elimination pathway with less than 1% of the dose recovered in the urine. Biliary elimination presumably accounts for a portion of the elimination as evidenced by biliary concentrations of albendazole sulfoxide similar to those achieved in plasma. Half Life: Terminal elimination half-life ranges from 8 to 12 hours (single dose, 400mg). Biological Half-Life Terminal elimination half-life ranges from 8 to 12 hours (single dose, 400mg). Albendazole ... is rapidly metabolized ... to albendazole sulfoxide, which ... has a highly variable plasma half-life ranging from about 4 to 15 hr ... Both /(+) and (-)/ sulfoxide derivatives are oxidized further to the nonchiral sulfone metabolite ... This reaction favors the (-) sulfoxide and probably becomes rate limiting in determining ... plasma half-life of the bioactive (+) sulfoxide metabolite. Induction of enzymes involved in sulfone formation from the (+) sulfoxide could account for some of the wide variation noted in plasma half-lives of albendazole sulfoxide. |
| Toxicity/Toxicokinetics |
Toxicity Summary 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. 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 and recovery is distinctively rapid once the drug is stopped. 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. Likelihood score: B (highly likely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Albendazole and its active metabolite are minimally excreted into breastmilk. An informal consultation group to the World Health Organization concluded that a single oral dose of albendazole can be given to lactating women. ◉ Effects in Breastfed Infants Two mothers with intestinal parasites were given a single 400 mg oral dose of albendazole while exclusively breastfeeding their infants who were between 1 and 6 months of age. No mention was made of adverse reactions in the breastfed infants. ◉ Effects on Lactation and Breastmilk A study compared mothers in Peru who were given either a single dose of albendazole 400 mg (n = 117) or matching placebo (n = 99). Infant breastmilk intake was measured at 1 and 6 months postpartum. At 1 month postpartum, 92.5% of subjects were exclusively or predominantly breastfeeding. Daily infant milk intake was 756 mL in the albendazole group and 774 mL in the placebo group, which was not statistically different. A 6 months, only 10% of each group was exclusively or predominantly breastfeeding. Their infants’ milk intakes were not statistically different. Protein Binding 70% bound to plasma protein Toxicity Data LD50: 1500 mg/kg (oral,mouse). [MSDS] Interactions 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. |
| References |
[1]. In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by albendazole. Cancer Lett. 2001 Apr 10;165(1):43-9. [2]. Regulation of apoptosis and autophagy by albendazole in human colon adenocarcinoma cells. Biochimie. 2022 Jul;198:155-166. [3]. Albendazole inhibits HIF-1α-dependent glycolysis and VEGF expression in non-small cell lung cancer cells. Mol Cell Biochem. 2017 Apr;428(1-2):171-178. [4]. Efficacy of novel albendazole salt formulations against secondary cystic echinococcosis in experimentally infected mice. Parasitology. 2020 Nov;147(13):1425-1432. [5]. Determination of albendazole and metabolites in silkworm Bombyx mori hemolymph by ultrafast liquid chromatography tandem triple quadrupole mass spectrometry. PLoS One. 2014 Sep 25;9(9):e105637. |
| Additional Infomation |
Therapeutic Uses Mesh Headings: anthelmintics, anticestodalagents, antiprotozoal agents Albendazole is a benzimidazole carbamate, used for the treatment of gastrointestinal infestations with roundworms, lungworms and tapeworms and adult flukes of Fasciola hepatica. Certain microsporidial species that cause intestinal infections in people with AIDS respond partially (Enterocytozoon bieneusi) or completely (Encephalitozoon intestintalis and related Encephalitozoon species) to albendazole; albendazole's sulfoxide metabolite appears to be especially effective against these parasites in vitro. MEDICATION: ...Used against nematode infections: Ascaris, Necator, Ancylostoma, Trichuris, Enterobius, and systemic nematodes such as Trichinella spiralis, Gnathostoma spinigerum, and larval Angiostrongylus cantonensis. In addition it is used against the larval stages of the cestodes Echinococcus granulosus and E. multilocularis and for treatment of neurocysticercosis caused by Taenia solium. For more Therapeutic Uses (Complete) data for ALBENDAZOLE (21 total), please visit the HSDB record page. Drug Warnings Leukopenia has occurred in less than 1% of patients receiving albendazole, and rarely, granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia have been reported. Therefore, blood counts should be performed at the start of, and every 2 weeks during, each 28-day treatment cycle. The manufacturer states that if decreases in the total leukocyte count occur, treatment with albendazole may be continued if the decreases are modest and do not progress. Because albendazole has been associated with mild to moderate increases of hepatic enzymes in about 16% of patients receiving the drug in clinical trials, and may cause hepatotoxicity, liver function tests should be performed prior to each course of albendazole therapy and at least every 2 weeks during treatment with the drug. If clinically important increases in liver function test results occur, albendazole should be discontinued. The drug can be reinstituted when liver enzymes return to pretreatment levels, but laboratory tests should be performed frequently during repeat therapy. Albendazole may cause harm to the fetus and should be used during pregnancy only if the benefits justify the risk to the fetus and only in clinical circumstances where no alternative management is appropriate. Women of childbearing age should begin treatment only after a negative pregnancy test, and should be cautioned against becoming pregnant while receiving albendazole or within 1 month of completing treatment with the drug. Teratogenic in animals (rats and rabbits) and is not recommended in pregnancy or in infants younger than 2 years. For more Drug Warnings (Complete) data for ALBENDAZOLE (9 total), please visit the HSDB record page. Pharmacodynamics Albendazole is a broad-spectrum anthelmintic. The principal mode of action for albendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (7.54 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2 mg/mL (7.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7689 mL | 18.8445 mL | 37.6889 mL | |
| 5 mM | 0.7538 mL | 3.7689 mL | 7.5378 mL | |
| 10 mM | 0.3769 mL | 1.8844 mL | 3.7689 mL |