Metabolic fate of clentiazem in rats after consecutive oral administration. Plasma and tissue distribution and metabolites in plasma and brain.

Abstract

The tissue distribution of radioactivity and the presence of metabolites in plasma and brain were studied in male and female rats after single and consecutive oral administration of 14C-clentiazem at a dose of 30mg/kg. The plasma levels of radioactivity in male and female rats attained steady levels since the third day after starting dosage. The organ and tissue levels of radioactivity in male rats at 1 and 6hr after single and consecutive administration were lower than those in female rats, but became higher at 24 and/or 72hr. The plasma concentrations of the acidic metabolites were higher in the male rats and those levels were raised by the consecutive administration, however, few acidic metabolites in the brain were found. Basic metabolites were more abundant in the brain and the level of the basic ones were higher in the female rats. The basic metabolite in the plasma and brain was mainly MB1 in the both sexes.