DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Albenza (Albendazole) - Description and Clinical Pharmacology

 
 



DESCRIPTION

ALBENZA (albendazole) is an orally administered broad-spectrum anthelmintic. Chemically, it is methyl 5-(propylthio)-2-benzimidazolecarbamate. Its molecular formula is C12H15N3O2S. Its molecular weight is 265.34. It has the following chemical structure:

Albendazole is a white to off-white powder. It is soluble in dimethylsulfoxide, strong acids, and strong bases. It is slightly soluble in methanol, chloroform, ethyl acetate, and acetonitrile. Albendazole is practically insoluble in water. Each white to off-white, film-coated tablet contains 200 mg of albendazole.

Inactive ingredients consist of: carnauba wax, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, sodium saccharin, sodium starch glycolate, and starch.

CLINICAL PHARMACOLOGY

Pharmacokinetics

Absorption and Metabolism

Albendazole is poorly absorbed from the gastrointestinal tract due to its low aqueous solubility. Albendazole concentrations are negligible or undetectable in plasma as it is rapidly converted to the sulfoxide metabolite prior to reaching the systemic circulation. The systemic anthelmintic activity has been attributed to the primary metabolite, albendazole sulfoxide. Oral bioavailability appears to be enhanced when albendazole is coadministered with a fatty meal (estimated fat content 40 g) as evidenced by higher (up to 5-fold on average) plasma concentrations of albendazole sulfoxide as compared to the fasted state.

Maximal plasma concentrations of albendazole sulfoxide are typically achieved 2 to 5 hours after dosing and are on average 1.31 mcg/mL (range 0.46 to 1.58 mcg/mL) following oral doses of albendazole (400 mg) in 6 hydatid disease patients, when administered with a fatty meal. Plasma concentrations of albendazole sulfoxide increase in a dose-proportional manner over the therapeutic dose range following ingestion of a fatty meal (fat content 43.1 g). The mean apparent terminal elimination half-life of albendazole sulfoxide typically ranges from 8 to 12 hours in 25 normal subjects, as well as in 14 hydatid and 8 neurocysticercosis patients.

Following 4 weeks of treatment with albendazole (200 mg three times daily), 12 patients’ plasma concentrations of albendazole sulfoxide were approximately 20% lower than those observed during the first half of the treatment period, suggesting that albendazole may induce its own metabolism.

Distribution

Albendazole sulfoxide is 70% bound to plasma protein and is widely distributed throughout the body; it has been detected in urine, bile, liver, cyst wall, cyst fluid, and cerebral spinal fluid (CSF). Concentrations in plasma were 3- to 10-fold and 2- to 4-fold higher than those simultaneously determined in cyst fluid and CSF, respectively. Limited in vitro and clinical data suggest that albendazole sulfoxide may be eliminated from cysts at a slower rate than observed in plasma.

Metabolism and Excretion

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. Following oral administration, albendazole has not been detected 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.

Special Populations

Patients with Impaired Renal Function

The pharmacokinetics of albendazole in patients with impaired renal function have not been studied. However, since renal elimination of albendazole and its primary metabolite, albendazole sulfoxide, is negligible, it is unlikely that clearance of these compounds would be altered in these patients.

Biliary Effects

In patients with evidence of extrahepatic obstruction (n = 5), the systemic availability of albendazole sulfoxide was increased, as indicated by a 2-fold increase in maximum serum concentration and a 7-fold increase in area under the curve. The rate of absorption/conversion and elimination of albendazole sulfoxide appeared to be prolonged with mean Tmax and serum elimination half-life values of 10 hours and 31.7 hours, respectively. Plasma concentrations of parent albendazole were measurable in only 1 of 5 patients.

Pediatrics

Following single-dose administration of 200 mg to 300 mg (approximately 10 mg/kg) albendazole to 3 fasted and 2 fed pediatric patients with hydatid cyst disease (age range 6 to 13 years), albendazole sulfoxide pharmacokinetics were similar to those observed in fed adults.

Elderly Patients

Although no studies have investigated the effect of age on albendazole sulfoxide pharmacokinetics, data in 26 hydatid cyst patients (up to 79 years) suggest pharmacokinetics similar to those in young healthy subjects.

Microbiology

The principal mode of action for albendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.

In the specified treatment indications albendazole appears to be active against the larval forms of the following organisms:

Echinococcus granulosus

Taenia solium

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017