Fenbendazole (Methyl 5-(phenylthio)-2-benzimidazolecarbamate)

Fenbendazole

Other Names: Methyl 5-(phenylthio)-2-benzimidazolecarbamate, Fenbendazol, Phenbendasol, HOE 881
Chemical Formula: C₁₅H₁₃N₃O₂S
Molar Mass: 299.35 g/mol
CAS Number: 43210-67-9
SMILES: COC(=O)NC1=NC2=C(N1)C=C(C=C2)SC3=CC=CC=C3
Appearance: White to light brownish-gray crystalline powder
Odor: Not specifically characterized in standard scientific references

Fenbendazole is a benzimidazole carbamate compound containing a benzimidazole ring substituted with a phenylthio group and a methyl carbamate functionality. It belongs to the benzimidazole class of anthelmintic compounds and is extensively studied in veterinary pharmacology, parasitology and medicinal chemistry. Its biological activity is closely associated with interaction with parasite tubulin, resulting in disruption of microtubule formation and cellular processes dependent on an intact microtubule network. Fenbendazole is also an important model compound for investigations of benzimidazole resistance, metabolism and drug-delivery systems.

Chemical and physical properties

Fenbendazole is a crystalline solid with a molecular mass of 299.35 g/mol. Experimental data report a melting point of approximately 233 °C, with decomposition occurring around the melting region. Its aromatic benzimidazole and phenylthio groups contribute to substantial hydrophobic character, while the carbamate and benzimidazole nitrogen atoms provide sites capable of intermolecular hydrogen-bonding interactions.

Fenbendazole has very low aqueous solubility. Experimental database values report a solubility of approximately 0.9 µg/mL at pH 7.4. This limited water solubility is an important physicochemical characteristic influencing dissolution and bioavailability and has motivated extensive research into alternative formulations, nanocrystals, cyclodextrin complexes and amorphous solid dispersions.

Experimental equilibrium-solubility studies have demonstrated that fenbendazole solubility increases with temperature and is strongly dependent on solvent composition. Studies involving aqueous mixtures of methanol, ethanol, ethylene glycol and N,N-dimethylformamide showed substantially enhanced solubility in the presence of organic co-solvents. X-ray powder diffraction analysis indicated that the crystalline material remained structurally unchanged during these equilibrium measurements.

Fenbendazole undergoes oxidative metabolism, principally forming fenbendazole sulfoxide, also known as oxfendazole, followed by further oxidation to fenbendazole sulfone. The sulfoxide metabolite retains anthelmintic activity, and the metabolism and pharmacokinetics of these compounds have been extensively investigated in veterinary pharmacology.

Applications

Fenbendazole is widely used in veterinary medicine as a broad-spectrum benzimidazole anthelmintic. Its principal biochemical mechanism involves interaction with parasite β-tubulin and inhibition of normal microtubule formation. Microtubules are essential for intracellular transport, cell division and other cellular processes, and disruption of their function contributes to the antiparasitic activity of benzimidazole compounds.

In parasitology research, fenbendazole is used as a model benzimidazole compound for studying mechanisms of anthelmintic susceptibility and resistance. Tubulin-binding experiments with susceptible and resistant strains of Haemonchus contortus have demonstrated differences in high-affinity benzimidazole-binding sites, supporting the central role of tubulin in both drug activity and resistance mechanisms.

Fenbendazole is also employed in pharmacokinetic and drug-metabolism research. Analytical studies frequently determine fenbendazole together with its sulfoxide and sulfone metabolites in biological matrices in order to investigate absorption, distribution, biotransformation and elimination.

Because of its exceptionally low water solubility, fenbendazole is frequently used as a model poorly soluble compound in pharmaceutical formulation research. Nanocrystals, cyclodextrin complexes, co-solvent systems, spray-dried dispersions and other formulation technologies have been investigated to increase its dissolution rate and apparent solubility.

Fenbendazole is additionally used as an analytical reference compound in chromatographic and mass-spectrometric methods developed for benzimidazole compounds and their metabolites. Its defined molecular structure and characteristic oxidative metabolites make it useful for method development, validation and comparative metabolic studies.

Scientific references

• PubChem. Fenbendazole, CID 3334. National Center for Biotechnology Information. Molecular formula, molecular weight, CAS number, structural identifiers, physicochemical properties and SMILES.
• Lubega, G. W.; Prichard, R. K. Specific interaction of benzimidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in Haemonchus contortus. Molecular and Biochemical Parasitology, 1990, 38(2), 221–232. DOI: 10.1016/0166-6851(90)90025-H.
• McKellar, Q. A.; Harrison, P.; Galbraith, E. A.; Inglis, H. Pharmacokinetics of fenbendazole in dogs. Journal of Veterinary Pharmacology and Therapeutics, 1990, 13(4), 386–392. DOI: 10.1111/j.1365-2885.1990.tb00793.x.
• Zhang, J.; Huang, C.; Chen, J.; Xu, R. Equilibrium Solubility Determination and Modeling of Fenbendazole in Cosolvent Mixtures at (283.15–328.15) K. Journal of Chemical & Engineering Data, 2019, 64(9), 4095–4102. DOI: 10.1021/acs.jced.9b00471.
• Melian, M. E.; Ibarra, M.; Ceballos, L.; Paredes, A. J.; Munguía, B.; Faccio, R.; Palma, S.; Álvarez, L. I.; Domínguez, L. Improving the in vitro dissolution rate and pharmacokinetic performance of fenbendazole in sheep using drug nanocrystals. Research in Veterinary Science, 2022. DOI: 10.1016/j.rvsc.2021.12.001.
• Cray, C.; Altman, N. H. An Update on the Biologic Effects of Fenbendazole. Comparative Medicine, 2022, 72(4), 215–219. DOI: 10.30802/AALAS-CM-22-000006.
• McKellar, Q. A.; Scott, E. W. The benzimidazole anthelmintic agents – a review. Journal of Veterinary Pharmacology and Therapeutics, 1990, 13(3), 223–247. DOI: 10.1111/j.1365-2885.1990.tb00773.x.

Safety:

Uwaga Zwroty wskazujące rodzaj zagrożenia : H361fd Podejrzewa się, że działa szkodliwie na płodność. Podejrzewa się, że działa szkodliwie na dziecko w łonie matki. H373 Może powodować uszkodzenie narządów (Wątroba, węzeł chłonny, Żołądek, Układ nerwowy) poprzez długotrwałe lub narażenie powtarzane. H410 Działa bardzo toksycznie na organizmy wodne, powodując długotrwałe skutki. Zwroty wskazujące środki ostrożności : Zapobieganie: P202 Nie używać przed zapoznaniem się i zrozumieniem wszystkich środków bezpieczeństwa. P260 Nie wdychać pyłu. P273 Unikać uwolnienia do środowiska. P280 Stosować rękawice ochronne/ odzież ochronną/ ochronę oczu/ ochronę twarzy. Reagowanie: P308 + P313 W przypadku narażenia lub styczności: Zasięgnąć porady/ zgłosić się pod opiekę lekarza. P391 Zebrać wyciek.

Storage:

Store the product in a tightly closed container in a cool, dry and well-ventilated place.

Recommended storage temperature: 2–8°C.

Protect from moisture, contamination and direct sunlight.

Keep away from strong oxidising agents and incompatible materials.

Handling:

Avoid the formation and inhalation of dust.

Avoid contact with skin and eyes.

Use in a well-ventilated place.

During handling, use appropriate personal protective equipment, including protective gloves, eye protection and protective clothing.

The product is intended exclusively for technical, laboratory and research applications. It is not intended for consumption, medical, pharmaceutical, cosmetic or feed applications.