The distribution of [3H]synthanecine A bis-N-ethylcarbamate and its metabolites in the rat.

An intravenous dose of 40 mg/kg [3H] synthanecine A bis-N-ethylcarbamate, sufficient to cause liver lesions similar to pyrrolizidine alkaloid poisoning, was given to male rats. The distribution of radioactivity in body tissues was measured after various times from 2 h to 340 days. About 69% of the dose was eliminated via urine and faeces on the first day, while less than 0.4% was found in expired air. The highest tissue level of radioactivity was initially in liver, but this fell steadily at a rate comparable with most other tissues. High levels were also found in kidneys, spleen and lungs, and elimination from the latter was exceptionally slow. A high level in the erythrocytes probably accounted for a persistence of radioactivity in the spleen. Ehrlich estimations showed that 68% of the radioactivity in the liver 2--6 h after dosing was present as pyrrolic metabolites. A high proportion of the liver activity was not extractable by alcohol or aqueous trichloroacetic acid. Binding in the microsomal and nuclear fractions of liver was surprisingly low. From the low level of radioactivity in stomach tissue it was concluded that 2,3-bishydroxymethyl-1-methyl pyrrole could not have been a major metabolite in the bloodstream, since the latter, when given intravenously, binds strongly to the glandular stomach.