Abstract
The metabolites of cabergoline in liver were investigated in rats after a single oral administration. The identification was performed by HPLC and mass spectrometry equipped with an APCI interface. In addition to cabergoline, the identified metabolites are FCE-27395 which is the demethylated derivative of cabergoline and, possibly, one more demethylated of FCE-27395.
Analysis of the metabolites in liver after a single oral administration of [14C]-cabergoline (0.5 mg/kg) showed a difference in the content of the metabolites between male and female rats. This sexual difference was due to the much higher content in FCE-27395 in male rat liver compared to female rat liver. For both sexes the major metabolite was FCE-27395, and other metabolites were found in minor quantities.
The consecutive administration of cabergoline did not cause any induction of hepatic drug metabolizing enzymes, such as cytochrome P450, cytochrome b5, aniline hydroxylase, and aminopyrine demethylase.
The distribution in the brain after a single intravenous administration of [3H]-cabergoline (0.5 mg/kg) was also investigated. The collected tissues were cerebral cortex, striatum, and hypophysis. The highest radioactivity was in the hypophysis, in which tissue the radioactivity tended to remain until 24 hour after dosing. Most of the radioactivity in these tissues could be attributed to cabergoline, as there were only traces of its metabolites.
