Plasma mebendazole levels were analysed retrospectively in patients treated for inoperable infections with Echinococcus multilocularis or granulosus. In 10 patients receiving mebendazole at 4 dose levels there was no relation between dose and plasma concentration. In 17 patients followed on the same dose for more than 18 months, the plasma levels varied with individual coefficients of variation ranging from 27 to 72%. The data reveal the limitations of single measurements of plasma mebendazole and emphasize the need for repeated monitoring. Coadministration of phenytoin and carbamazepine seemed to lower plasma levels, presumably as a result of enzyme induction. It was not possible appreciably to raise the mebendazole concentrations by inhibition of drug metabolizing enzymes with cimetidine.
Since 1976 60 patients with inoperable alveolar echinococcosis caused by Echinococcus multilocularis were treated with high doses of mebendazole and examined at regular intervals prospectively according to our protocol regarding clinical course, liver function, morphology, immunologically and plasma mebendazole levels. The average duration of disease was 8(1-19) years, the average duration of chemotherapy was 4.25 (0.75-9) years. The long term results showed a correlation of the clinical course with the mean plasma mebendazole levels and the duration of chemotherapy, respectively. Death (n = 5) or transient progression of the disease process (n = 14) was observed primarily in patients with low plasma mebendazole levels in the early course and within the first two years of chemotherapy. Only 9 patients showed a decrease of the parasite mass. Immundiagnosis (total serum IgE and serum antibodies against Echinococcus antigen) gave some information with regard to therapy results, but only in the long-term course. The cumulative survival of the patients under study was 96% at 5 years and 84% at 10 years, respectively which is markedly higher compared to historical control series with a letality of greater than 90% within 10 years.
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