Metabolism of a novel nitrosourea, tauromustine, in the rat.

A novel nitrosourea, 1-(2-chloroethyl)-3-[2-(dimethylaminosulphonyl)ethyl]1-nitrosourea , tauromustine (TCNU), has been investigated for in vitro metabolism by different rat organs. Two kinds of reactions were seen, demethylation and denitrosation, both reactions required NADPH. These reactions were achieved by the liver microsomes and to a much lesser extent by lung microsomes. Induction of cytochrome P450 system with phenobarbital resulted in increased demethylation (10 times) and denitrosation (6 times) of tauromustine while induction with 3-methylcholanthrene did not have any significant effect on these reactions. Known inhibitors of different cytochrome P450 activities inhibited the demethylation and denitrosation of tauromustine to different levels. After oral administration of [14C]tauromustine a metabolic pattern similar to that observed in vitro experiments, was seen in the urine. The demethylated compound, which has alkylating cytotoxic activity, could be detected in the urine up to 8 hr after oral administration.