The disposition of [¹⁴C]iprindole in man, dog, miniature swine, rhesus monkey and rat

Abstract

1. Absorption of a single oral dose of [¹⁴C]iprindole was rapid in rats, rhesus monkeys, miniature swine, dogs and human volunteers. In all species except the rat, most of the radioactivity in the blood resided in the plasma. Small amounts of unchanged iprindole were detected in the plasma of rats and rhesus monkeys but not in man and miniature swine.

2. Radioactivity was excreted mainly in the urine of man, miniature swine and rhesus monkey, but in the faeces of rat and dog.

3. Urinary radioactivity was associated with basic (free and conjugated), acidic and highly polar, water soluble metabolites. At least 20 metabolites as well as small amounts of unchanged drug were detected in the basic fractions of each species' urine.

4. Many of these metabolites were common to all species; however, qualitative as well as quantitative differences were apparent. Mass-spectrometric analysis of several metabolites indicated N-demethylation and oxidation of the alicyclic ring or a combination of both pathways.