Metabolism of the schistosomicidal agent hycanthone by rats and rhesus monkeys.

Abstract

The absorption, distribution, and excretion of hycanthone were studied with rats and rhesus monkeys using tritiated materials at the therapeutic dose recommended for man (3.0+/-0.5 mg/kg). Nine pairs of each species received single intramuscular doses of randomly tritiated (specific activity 193.7 mCi/mmol) hycanthone methanesulfonate and were then sacrificed at intervals between 15 min and 72 h after medication. Peak blood and tissue concentrations occurred 30-60 min after administration (plasma half-life-45 min). The highest concentrations were observed in the liver, spleen, kidneys and adrenals, but decreased rapidly (more than 80% of the dose was excreted in 48-72 hours). In monkeys a high concentration of the compound was found in the bile (hours 1-8), probably conjugated to glucuronic acid.Radiochromatography showed only unchanged drug in the blood and tissues, except in the liver where rapid conversion occurred to sulfoxide in the rat and to the deethyl analogue in the monkey.