Albendazole (Albenza®)
Albendazole
Brand Name: Albenza®
Classification:
Antiinfective Agents
Description: Albendazole (methyl 5-(propylthio)-2-benzimidazolecarbamate) is an oral broad-spectrum anthelmintic antiparasitic agent of the benzimidazole class. Albendazole is similar to mebendazole and thiabendazole, but is better tolerated. The systemic anthelmintic activity is attributed to albendazole sulfoxide, the primary active hepatic metabolite. Albendazole is effective in eradicating infections caused by a variety of nematodes including Echinococcus granulosus (dog tapeworm), Taenia saginata (beef tapeworm), Taenia solium (pork tapeworm), Trichinella spiralis (pork worm), Trichuris trichiura (whipworm), Enterobius vermicularis (pinworm), Strongyloides stercoralis (threadworm), Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), and Necator americanus (hookworm). Albendazole is currently the treatment of choice for treating hydatid cyst disease (larval stage E. granulosus infection), for which it is roughly 70% effective. In sheep-raising areas of Utah, Arizona, and Nevada, E. granulosus is considered to be endemic; however, annual infection rates are low and most human cases in the US occur in immigrants who were exposed in their countries of origin, or in US travelers visiting global endemic areas. Albendazole is also very effective (> 80%) for cysticercosis secondary to T. solium; neurocysticercosis is rare in the US except in immigrants from endemic areas. Albendazole is the only agent used for the treatment of ocular neurocysticercosis. The drug has also shown considerable efficacy in treating microsporidiosis caused by Septata intestinalis. Albendazole was first marketed outside the US in 1982, and common trade names in other countries include Eskazole® and Zentel®. In the US, albendazole (Albenza®) was FDA-approved for treating hydatid cyst disease and neurocysticercosis in June 1996.
Mechanism of Action: Benzimidazole antihelmintic agents inhibit the polymerization of tubulin and the microtubule-dependent uptake of glucose by binding free ?-tubulin. Albendazole selectively damages cytoplasmic microtubules in the absorptive and intestinal cells of nematodes but not of the host. This microtubular deterioration is irreversible and leads to disruption of absorptive and secretory functions of the cells, which are essential to the organism’s survival. This disruption results in accumulation of secretory substances in the Golgi apparatus, decreased glucose uptake, and depleted endogenous glycogen stores in the helminth. Due to diminished energy production the parasite is immobilized and eventually dies. Albendazole is larvicidal in necatoriasis and ovicidal in ascariasis, ancylostomiasis, and trichuriasis. Resistance to albendazole has been documented in animals and is due to loss of affinity to tubulin binding sites.
In general, the following organisms are susceptible to albendazole: Echinococcus granulosus (dog tapeworm), Taenia saginata (beef tapeworm), Taenia solium (pork tapeworm), Trichinella spiralis (pork worm), Trichuris trichiura (whipworm), Enterobius vermicularis (pinworm), Strongyloides stercoralis (threadworm), Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), and Necator americanus (hookworm).
 Albenza Tablets(Tab 200 mg)
Pharmacokinetics: Albendazole is administered orally as an immediate release tablet. Following oral administration, albendazole is poorly absorbed from the GI tract. To increase bioavailability it is recommended to give albendazole with a 40 g fat containing meal; the absorption of albendazole increases between 5 to 6.5-fold compared to when given with a non-fatty meal. Grapefruit juice also increases albendazole’s oral bioavailability (see Drug Interactions). Following oral administration, albendazole undergoes significant first pass metabolism to albendazole sulfoxide, the primary active metabolite. After an oral dose of 15 mg/kg, peak plasma levels of albendazole reach 0.045 - 0.296 mg/L. After an oral dose of albendazole 400 mg, peak plasma levels of albendazole sulfoxide reach 0.04 - 0.55 mg/L with great variation between individuals. In the treatment of hydatid disease, tissue concentrations of albendazole sulfoxide > 0.5 mg/L are required for therapeutic efficacy. Albendazole sulfoxide is 70% protein bound and has a half life (T1/2) of roughly 9 hours. Concentrations in CSF and brain tissue are 50% and 40%, respectively, of plasma concentrations. Echinococcal cyst concentrations are roughly 25% those of plasma. Albendazole is extensively metabolized by the liver. Albendazole induces cytochrome P450 1A enzymes and may induce its own metabolism. The primary elimination route is the bile. Renal elimination is negligible (< 1%).
Special Populations: Albendazole plasma concentrations increase significantly in patients with hepatic disease. In 5 patients with evidence of extrahepatic biliary obstruction, the maximum serum concentration and AUC of albendazole were increased by 2-fold and 7-fold, respectively. Since renal elimination of albendazole and its primary metabolite is negligible, it is unlikely that renal impairment alters the clearance of these agents. The pharmacokinetics of the drug in children (aged >= 6 years) at doses of 10 mg/kg PO are similar to those of adults. Limited data suggest similar pharmacokinetics in the elderly as compared to younger adults.
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References
. Liu LX, Weller PF. Antiparasitic drugs. N Engl J Med 1996;334:1178 - 84.
. Nagy J, Schipper HG, Koopmans RP, et al. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 2002;66:260 - 3.
. Venkatesan P. Albendazole. J Antimicrob Chemother 1998;41:145 - 7.
[ Revised 4/1/2004 11:27:00 AM ]
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