Chemotherapy of larval echinococcosis with mebendazole: microsomal liver function and cholestasis as determinants of plasma drug level

Abstract

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis, possibly due to an inadequate plasma concentration of the drug in some patients. In order to improve therapeutic results the influence of liver function on the plasma levels of mebendazole was investigated during long term therapy. Plasma mebendazole concentrations measured before the morning dose (trough values) showed a highly significant, negative correlation both with the aminopyrine breath test (ABT; rs = -0.78, n = 14, p less than 0.001) and the second exponential component of bromsulphthalein elimination (BSP- k2; rs = -0.74, n = 12, p less than 0.01). These relationships also applied over longer than a single day, since trough and peak mebendazole levels observed over an interval of 6 months before and after testing liver function were equally well correlated with ABT and BSP-k2. The daily dosage and other liver function tests seemed to be of minor importance in determining the plasma levels. It was concluded that the microsomal function of the liver and/or cholestasis might be important determinants of plasma mebendazole levels. The results of the study imply that higher and more effective mebendazole concentrations might be achieved by inhibition of the drug metabolizing capacity of the liver rather than by increasing the dose of mebendazole.