Abstract :

The history of medical treatment of echinococcosis is intimately related to development and use of benzimidazole carbamates (e.g., mebendazole, albendazole, etc.) as a safe and effective class of anti-parasitic drugs. The most important side effects include abnormality in liver enzymes, hair loss, drug allergy, bone marrow suppression. Factors predicting the cyst's response to treatment are size, site and dosage and method of use of the drug. Relapses occur in 3-25% of patients, the majority occurs within first two years. There are a few contraindications to the medical therapy of hydatid cyst, including: pregnancy, bone marrow suppression, liver diseases, diabetes mellitus and some cyst characteristics such as size and location of some of cysts.

Introduction :

Treatment of cystic echinococcosis changed substantially during the past 20 years. Although surgery is still considered the first choice approach for radical care (1-3), medical treatment - both as adjunct and as sole treatment and also minimally invasive puncture techniques under sonographic and CT guidance gain increasing acceptance. Surgical treatment of the hydatid cysts have an inherent paradox, i.e. radical surgical procedures that have substantially less incidence of recurrences also are associated with increased morbidity, mortality, post-operative complications and hospital stay. Such invasive procedures are also impossible in substantial proportion of the patients because of co-morbid diseases, presence of multiple cysts in one or multiple organs and proximity of the cysts to major vascular or biliary structures.(2)

Mebendazole :

Mebendazole is available as 100mg tablets. The drug is only slightly soluble in water and poorly absorbed after oral administration.(4-6) The rate of absorption increases (up to 8 folds) if the drug is taken during a meal specially one with a high fat content.(1,5) In plasma more than 95% of the drug is protein-bound.(5,6) Mebendazole is rapidly metabolized in liver to inactive metabolites, which are excreted via bile and urine. (1,5,6) It seems that the mebendazole itself rather than its metabolite is the active drug. (5,7) The elimination half-life is short (2.5-5.0 hours) but may be increased in patients with cholestasis. (5,7) The serum level of the drug show great inter-individual variability and not correlate with the dose given but serum level 4 hours after the morning dose have a high degree of predictability for the 24-hour average serum concentration. (1,7) Based on animal studies and therapeutic trials in human, the serum level of 200-250 nmol/L 4 hours after the morning dose is suggested as the required concentration for anti-echinococcal effect (1,7), however several studies showed that such concentrations may not be attained by more than 30% of patients and lower (yet undetermined) levels may be sufficient. (1) Mebendazole have minimal and mild side effects when used in low doses and for short courses (e.g.: 100mg bid for 3 days) including mild abdominal pain and diarrhea in those with high intestinal parasite burdens. (6) When the drug is used in high doses and for prolonged duration as in the treatment of echinococcosis, about 2/3 of patients experience one or more side-effects but they are mostly of minor severity and importance. (1) The more important side effects include: alopecia, liver enzyme abnormalities and bone marrow suppression (with severe but reversible neutropenia). (6)

Albendazole :

Albendazole (methyl-S-N- propoxy thio- 2- benzimidazole carbamate) has an exceptionally broad spectrum of anti-parasitic activity. (5,6) The drug is a white, odorless powder dispensed as 400mg human or 600mg veterinary tablets. It is practically insoluble in water and has erratic and variable absorption after oral administration. As for mebendazole the absorption of the drug can be enhanced by administration with a fatty meal. (5,6,8) Albendazole undergoes extensive first-pass metabolism in the liver and only albendazole sulfoxide which is primarily responsible for anti-helminthic effect can be detected in serum. (5,6,8) The peak serum concentration of albendazole sulfoxide is reached within 2-4 hours following oral consumption. (7) It has plasma half-life of 9 hours and is 70% protein bound. (5,8) Albendazole sulfoxide is further oxidized to inactive sulfon metabolite. (5) The drug induces the cytochrome P450 responsible for its own metabolism and co-administration of cimetidine increases the serum levels. (8) It is also shown in animal experiments that co-administration of cimetidine and albendazole may increase the therapeutic effect on alveolar echinococcosis. (9) Co-administration of dexamethasone also increases the serum levels of Albendazole. (6) No human studies done to elucidate the incidence and clinical significance of albendazole resistance in hydatid cysts. Although about 2/3 of the patients experience one or more side-effects, they are mostly of little importance and reversible (1,4,7,8,) and only in about 2.6 to 3.8 % of patients, drug was discontinued because of the side-effects such as elevated serum transaminases, bone marrow suppression or alopecia. (4,7)