Originator
Zentel ,SK and F ,France ,1981
Definition
ChEBI:Albendazole is a carbamate ester that is methyl 1H-benzimidazol-2-ylcarbamate substituted by a propylsulfanyl group at position 5. It is commonly used in the treatment of parasitic worm infestations. It has a role as a tubulin modulator, a microtubule-destabilising agent and an anthelminthic drug. It is a carbamate ester, a benzimidazolylcarbamate fungicide, an aryl sulfide and a member of benzimidazoles.
Manufacturing Process
A mixture of 6.65 g of 3-chloro-6-nitroacetanilide, 3.2 ml of propylmercaptan,
5.6 g of 50% sodium hydroxide and 100 ml of water is heated at reflux
overnight. The cooled mixture is filtered to give the desired 2-nitro-5-
propylthioaniline, MP 69.5-71.5°C after recrystallization from ethanol then
hexane-ether. NMR (CDCl3) 40%.
The aniline (2.5 g) is hydrogenated with 1.9 ml of concentrated hydrochloric
acid, 100 ml ethanol and 5% palladium-on-charcoal to give 4-propylthio-ophenylene-
diamine hydrochloride.
A mixture of 2.5 ml of 50% sodium hydroxide in 5 ml of water is added to a
mixture of 1.9 g of cyanamide, 2.2 g of methylchloroformate, 3.5 ml of water
and 3 ml of acetone over 45 minutes below 10°C, pH raised to 6.5. A molar
equivalent solution of the diamine in 100 ml of ethanol is added. The mixture
is heated until the easily volatile solvents are expelled, to about 85°C, then
maintained at this temperature with some water added for one-half hour. The
product, methyl 5-propylthio-2-benzimidazolecarbamate, is separated, washed
to give a colorless crystalline solid, MP 208-210°C.
Brand name
Albenza (GlaxoSmithKline).
Therapeutic Function
Anthelmintic
Antimicrobial activity
Albendazole is active against trichostrongyles
and exhibits useful activity against tissue-dwelling larvae
of Trichinella spiralis, larvae of animal hookworms (causing
cutaneous larva migrans) and microfilariae of various filarial
species. It also exhibits some activity against cysticercosis and
hydatid stages of Echinococcus granulosus and Echinococcus
multilocularis. It has been successfully used in infections with
the protozoon Giardia lamblia and for microsporidiosis.
General Description
Chemical structure: benzimidazole
Pharmaceutical Applications
A benzimidazole carbamic acid methyl ester available for oral
administration. Insoluble in water, soluble in dimethyl sulfoxide.
Stable at room temperature.
Biochem/physiol Actions
Binds to tubulin and inhibits microtubule assembly.
Mechanism of action
Albendazole is given orally and is poorly and variably
absorbed (5%) because of its poor water solubility.
Oral bioavailability is increased as much as five
times when the drug is given with a fatty meal instead of
on an empty stomach. Concurrent treatment with corticosteroids
increases plasma concentrations of albendazole.
The drug is rapidly metabolized in the liver to an
active sulfoxide metabolite.The half life of the metabolites
is 8 to 12 hours.
Pharmacokinetics
Albendazole is better absorbed after oral absorption than
other benzimidazole carbamates. It is extensively metabolized
to the anthelmintically active albendazole sulfoxide,
producing plasma concentrations of the metabolite
of about 1.3 mg/L 2–5 h after a 400 mg oral dose. The
half-life is about 8 h and the major route of excretion is
via the bile. Plasma protein binding of the sulfoxide is
around 70%.
Clinical Use
Albendazole has a broad spectrum of activity against
intestinal nematodes and cestodes, as well as the liver
flukes Opisthorchis sinensis, Opisthorchis viverrini, and
Clonorchis sinensis. It also has been used successfully
against Giardia lamblia. Albendazole is an effective treatment
of hydatid cyst disease (echinococcosis), especially
when accompanied with praziquantel. It also is effective
in treating cerebral and spinal neurocysticercosis, particularly
when given with dexamethasone.Albendazole is recommended
for treatment of gnathostomiasis.
Clinical Use
Intestinal worm infections
Trichinosis (including chronic stage)
Cutaneous larva migrans
Hydatid disease (as an adjunct, or alternative, to surgery)
Neurocysticercosis
Lymphatic filariasis (alone or in combination with ivermectin)
Giardiasis
Microsporidiosis
Clinical Use
Methyl 5-(propylthio)-2-benzimidazolecarbamate (Eskazole,Zentel) is a broad-spectrum anthelmintic that is not currentlymarketed in North America. It is available from the manufactureron a compassionate use basis. Albendazole is widelyused throughout the world for the treatment of intestinalnematode infection. It is effective as a single-dose treatmentfor ascariasis, New and Old World hookworm infections,and trichuriasis. Multiple-dose therapy with albendazole caneradicate pinworm, threadworm, capillariasis, clonorchiasis,and hydatid disease. The effectiveness of albendazole againsttapeworms (cestodes) is generally more variable and lessimpressive.
Albendazole occurs as a white crystalline powder that isvirtually insoluble in water. The oral absorption of albendazoleis enhanced by a fatty meal. The drug undergoes rapidand extensive first-pass metabolism to the sulfoxide, whichis the active form in plasma. The elimination half-life ofthe sulfoxide ranges from 10 to 15 hours. Considerable biliaryexcretion and enterohepatic recycling of albendazolesulfoxide occurs. Albendazole is generally well toleratedin single-dose therapy for intestinal nematodes. The highdose,prolonged therapy required for clonorchiasis orechinococcal disease therapy can result in adverse effectssuch as bone marrow depression, elevation of hepatic enzymes,and alopecia.
Synthesis
Albendazole, methyl-[5-(propylthio)-1H-benzoimidazol-2-yl]carbamate
(38.1.18), is also made by the heterocyclization of a derivative of phenylenediamine to a
derivative of benzimidazole. In order to do that, 3-chloro-6-nitroacetanylide is reacted
with propylmercaptane to make 3-propylthio-6-nitroacetanylide (38.1.6). Reducing the
nitro group in this compound with hydrogen using a palladium on carbon catalyst
gives 4-(propylthio)-o-phenylenediamine (38.1.7). Reacting the resulting derivative of
o-phenylenediamine with cyanamide and then with the methyl chloroformate gives the
desired albendazole.
Veterinary Drugs and Treatments
Albendazole is labeled for the following endoparasites of cattle (not
lactating): Ostertagia ostertagi, Haemonchus spp., Trichostrongylus
spp., Nematodius spp., Cooperia spp., Bunostomum phlebotomum,
Oesphagostomum spp., Dictacaulus vivaparus (adult and 4th stage
larva), Fasciola hepatica (adults), and Moniezia spp.
In sheep, albendazole is approved for treating the following
endoparasites: Ostertagia circumcincta, Marshallagia marshalli,
Haemonchus contortus, Trichostrongylus spp., Nematodius spp.,
Cooperia spp., Oesphagostomum spp., Chibertia ovina, Dictacaulus
filaria, Fasciola hepatica, Fascioides magna, Moniezia expansa, and
Thysanosoma actinoides.
Albendazole is also used (extra-label) in small mammals, goats
and swine for endoparasite control.
In cats, albendazole has been used to treat Paragonimus kellicotti
infections. In dogs and cats, albendazole
has been used to treat
capillariasis. In dogs, albendazole has been used to treat Filaroides
infections. It has been used for treating giardia infections in small
animals, but concerns about bone marrow toxicity have diminished
enthusiasm for the drug’s use.
