Metabolism of levamisole, an anti-colon cancer drug, by human intestinal bacteria

1. Anaerobic incubation of levamisole with human intestinal flora resulted in the formation of three thiazole ring-opened metabolites, namely, levametabol-I, II and III. These new hydroxamic lactam-type metabolites were isolated and characterized by various spectroscopic methods. 2. Various pure cultures of human intestinal bacterial strains were shown, by quantitative h.p.l.c. analysis, to have ring-opening ability. Strong metabolizers include Bacteroides and Clostridium spp. Bacterial mixtures prepared from human faeces showed much greater ability to transform levamisole (74% in 48 h) than any pure strain culture. 3. Greatly decreased levamisole-transforming activity was observed with autoclaved bacterial cultures, and no activity was found with broth medium alone. This indicates that metabolism requires the presence of anaerobic bacteria and involves, at least in part, a non-enzymic process.