The biotransformation of [¹⁴C]minaprine in man and five animal species

Abstract

1. [¹⁴C]Minaprine was administered as a single oral dose to five animal species and to a healthy and informed volunteer. Excretion of radioactivity was followed during 48 h in urine and faeces; biliary excretion was followed only in rat.

2. Urinary metabolites were isolated and identified by mass spectrometry.

3. A quantitative comparison of metabolites in different species was made. On the basis of these data it is concluded that the dog is not a suitable model for man for pharmacological or toxicological studies.

4. The major metabolic route is 4-hydroxylation of the aromatic ring. The only unexpected metabolic route found was the biotransformation of the morpholino ring, probably by reductive ring-cleavage.

5. About 50% of the ¹⁴C was excreted in 0-48 h urine. The other 50% was excreted in the 0-48 h faeces. In the rat, this was attributed entirely to biliary excretion. The drug is well absorbed after oral administration and is not accumulated in the body.