Hepatotoxicity of mebendazole. Relationship with serum concentrations of the drug.

We report the case of a 47-year-old female patient, suffering from multiple hydatid cysts of the liver, in whom hepatitis developed after mebendazole treatment. Clinical manifestations of hypersensitivity were absent. A correlation was found between serum mebendazole concentrations and the degree of cytolysis; this is compatible with a direct hepatotoxic effect of mebendazole.

Cimetidine increases serum mebendazole concentrations. Implications for treatment of hepatic hydatid cysts.

In eight patients (five with peptic ulcer disease and three with hydatid cysts), the [14C]-aminopyrine breath test (ABT) and maximum serum concentration of mebendazole following a dose of 1.5 g of mebendazole three times daily were determined before and after treatment with cimetidine (400 mg three times daily for 30 days). Serum mebendazole concentrations were measured in blood samples taken 2 h after each drug intake. Cimetidine lowered the 14CO2 specific activity (SA) at 1 h (P less than 0.01) and increased the maximum serum concentration of mebendazole (P less than 0.01). A significant correlation was found between SA at 1 h and the highest concentration of mebendazole before (r = -0.71, P less than 0.05) and after (r = -0.82, P less than 0.05) cimetidine ingestion. Combined administration of cimetidine and mebendazole resulted in the complete resolution of previously unresponsive hydatid cysts.

Radiological changes under effect of mebendazole on univesicular hydatid cysts in the liver and lung.

Mebendazole was given to a patient who had developed four univesicular hydatid cysts in 16 months following initial infection (two in the liver and two in the lungs). The size of the cysts varied from five to ten centimeters in diameter. The therapeutic effect of the drug was assessed by ultrasound, computed tomography and chest x-ray examination. A completely split wall was only observed in the smallest hepatic cyst after a three-month period with a dose of 2.4 g per day (50 mg/kg/day). Peak serum level of mebendazole was 45.2 ng/ml. Thereafter, the intake was increased to 4.5 g per day (86.5 mg/kg/day) during one year. Peak drug serum level was 67.7 ng/ml. Dramatic radiological changes were subsequently noted in the other cysts. These radiological changes precisely mimicked those changes observed during the natural course of healthy cysts when they become complicated by ageing. We have found that ultrasound and chest x-ray proved to be the best method for assessing the therapeutic efficacy of medical treatment for univesicular cysts in the liver and lung. The asynchronous evolution observed in these lesions under such different drug schedules seems to depend on the size and location of the cyst, and on serum mebendazole levels as well as length of treatment.

A correlation between serum mebendazole concentrations and the aminopyrine breath test. Implications in the treatment of hydatid disease.

In 25 patients an [14C]-aminopyrine breath test (ABT) was performed immediately before the oral administration of 1.5-2 g of mebendazole three times daily. The concentration of mebendazole in serum was measured 2 h after each drug intake. A significant correlation was found between the results of ABT and the serum drug concentrations obtained after the second and third intake, as well as the highest concentration value. The ABT was repeated in six patients during a continuous treatment with mebendazole. In all of them this test indicated an increase in 14CO2 production with continued treatment. The results support the view that mebendazole is metabolized by the liver monooxygenase activity and behaves as an enzyme inducer.

Serum concentrations of mebendazole in patients with hydatid disease.

Mebendazole was administered to 22 patients, 17 of whom had developing or cured hydatid cysts, and to 5 volunteers. Then, at regular intervals, it was titrated by radioimmunoassay in the serum for 24 hours. Serum levels after the intake of 1 gram were perceptible on an empty stomach; they were higher when the drug was taken with a rich meal, but the difference was not statistically significant. The administration of increasing therapeutic doses (3, 4.5, 6 and 12 g a day) led to a concomitant increase of the average serum levels of mebendazole; concentrations varied between a minimum of 7.6 ng/ml and a maximum of 483 ng/ml. The difference between the various average concentrations was only significant after 8 hours when increasing from 3 to 6 g a day. The absence of a significant difference for the other average concentrations was due to the large interindividual variations. However, analysis of the individual results shows an increase of the serum concentrations parallel with that of the dose in 10 out of 12 patients. The effect of the dose seems to vary with the patient and the dose received. Blood samples taken 2 hours after each of the 3 daily drug intakes could give more information as to the serum concentrations susceptible to influence the parasite. The drug's half life, lying between 3.3 and 11.5 hours in 5 patients, is longer in case of major hepatic dysfunction, due to established hepatopathy. During the monitoring of 7 patients, the average serum levels were comparable with or higher than the initial concentration.

[The immunological diagnosis of hydatidosis. 139 cases (author's transl)]. / Diagnostic immunologique de l'hydatidose. 139 observations.

Hydatidosis is not rare in France and often poses diagnostic problems to practitioners. In addition to classical clinical and radiological data, immunological methods provide at the present time reliable means of confirming the diagnosis and conducting post-therapeutic surveillance. After a brief epidemiological and clinical review, the authors review the different laboratory techniques available and report their experience involving 139 cases collected over a period of 2 years. Emphasis is placed upon the relatively high prevalence of the disease amongst immigrant workers, as oppossed to the rare cases seen in the native population, as well as the value of immunoelectrophoresis and conditioned haemagglutination reactions. New therapeutic possibilities offered by mebendazole and its derivatives are indicated.

Domperidone in the treatment of functional dyspepsia in patients with delayed gastric emptying.

Forty patients who were suffering from chronic dyspepsia, diagnosed clinically and radiologically as being related to delayed gastric emptying, were treated with either domperidone or placebo in a double-blind trial. The trial lasted four weeks and the dose of domperidone was 10 mg orally t.d.s. before meals. The results showed that the drug markedly improved symptoms and that side effects were few, being recorded in one patient only, on active treatment. It is concluded that domperidone is a useful agent for the treatment of dyspepsia with retarded gastric emptying.

Treatment of hepatic hydatid disease with mebedazole: preliminary results in four cases.

Mebendazole was given to four patients with hepatic hydatid disease. In three patients hydatidosis had remained after surgery, and in the fourth it could not be treated surgically. Mebendazole was given orally in maximum doses of 400-600 mg three times a day during courses lasting 21 to 30 days. Ultrasonic echotomography showed a complete regression of the intrahepatic cysts after four to 13 months in all four cases. In three patients the course of treatment had to be repeated. Mebendazole also induced clinical improvement and a progressive lowering of the concentration of specific IgE of Echinococcus granulosus. During treatment circulating blood levels of specific immune complexes of antigen 5 were increased. These observations indicate that mebendazole has a lethal effect on E granulosus cysts in primary hydatid disease in man and that the efficacy of chemotherapy can be assessed with ultrasonography and by measuring changes in the concentration of specific IgE of E granulosus and circulating immune complexes.