Physiologic disposition of lergotrile.

ABSTRACT

Lergotrile, an ergot alkaloid, has been shown to be effective in treating disorders associated with elevated serum prolactin levels (e.g., galactorrhea-amenorrhea). Lergotrile has also been found to be a potent dopaminergic agonist and thus to be effective in Parkinson's disease. This study describes the physiologic disposition of lergotrile after administration to human volunteers. N-14CH3-lergotrile was rapidly absorbed from the gastrointestinal tract. Lergotrile was detected at low concentrations in plasma when subjects received large doses over extended periods of time. The major portion of radioactivity in plasma was attributed to the presence of circulating metabolites of lergotrile. Lergotrile metabolities were eliminated in the feces (ca. 60%), urine (ca. 20%), and breath (ca. 7% as 14CO2). A metabolite in feces was identified as 13-OH-lergotrile (up to 30% of the dose). A metabolite in urine was formed by conversion of the C8-acetonitrile group of lergotrile to a carboxyl group (about 10% of the dose). The presence of 14CO2 in the expired air after administering N-14C-methyl-lergotrile indicated that the drug was N-demethylated to form norlergotrile.