Powis G, Ames M M, Kovach J S
Cancer Res. 1979 Sep;39(9):3564-70.
Indicine N-oxide, a pyrrolizidine alkaloid N-oxide that exhibits antitumor activity without some of the toxic effects associated with other pyrrolizidine alkaloids, is metabolized to indicine in rabbits and humans. Indicine can be detected in the plasma and is excreted in the urine in a dose-dependent manner following the i.v. administration of indicine N-oxide. The p.o. administration of indicine N-oxide leads to an increased plasma concentration and an increased urinary excretion of indicine. The hepatic microsomal fraction and the gut flora both catalyze the anaerobic reduction of indicine N-oxide to indicine in vitro. Whole-animal studies suggest that the gut flora play a major role in the metabolic reduction of indicine N-oxide by the rabbit. Indicine N-oxide is not actively excreted in the bile, and it is probable that indicine N-oxide finds its way into the gut by passive diffusion following i.v. administration. Neomycin and erythromycin, which reduce the number of anaerobic bacteria in the gut, lead to decreased plasma levels and a decreased urinary excretion of indicine.
