Studies on the metabolic fate of azuletil sodium (II): Absorption, distribution, metabolism and excretion after single administration to mice and rats.

Abstract

The absorption, distribution, metabolism and excretion of 14C-KT1-32 were studied after a single oral and intravenous administrations in the doses of 4-100mg/kg to male and female rats, and male mice.1. The radioactivity in plasma reached a maximum concentration at 4.5hr (48μg equivalent KT1-32/ml) after oral administration of 14C-KT1-32 to male rats in a dose of 20mg/kg and then declined with half-life of 3.9hr.2. The levels of radioactivity in plasma reached a maximum concentration at 3.3hr after oral administration of 14C-KT1-32 to female rats in a dose of 20mg/kg and then declined with half-life of 3.7hr.3. The excretion of radioactivity amounted to 57% of the dose in urine and 43% of the dose in feces within 96hr after oral administration to male rats in a dose of 20mg/kg, while after intravenous administration to male rats, the excretion of radioactivity were found to be 81% and 17% of the dose in urine and feces, respectively.4. The biliary excretion within 48hr after oral administration of 20mg/kg corresponded to 7.7% of the administered dose to male rats, while the excretion of the radioactivity reabsorbed, amounted to 5.3% of the dose in the bile within 48hr after intraduodenal injection.5. After 20mg/kg oral administration, the female rats excreted during 96hr 73% and 28% of the dose in urine and feces, respectively.6. The radioactivities in the tissues, except the gastro -intestinal tract and fat, reached the maximum concentration at 3hr after oral administration of 20mg/kg to male rats and relatively high radioactivities were found in the blood, liver, kidney and lung. The radioactivities in all tissues were decreased to less than 17% of the highest concentration at 72hr after oral administration.7. In female rats, after oral administration of a dose of 20mg/kg, the concentrations in the tissues were lower than that in male rats.8. After oral administratrion of a dose of 20mg/kg, Ml, M2, M4 metabolites and the intact drug were the major components and M-3, M-5 and M-6 were also detected, however as the minor compounds, in the 0-24hr urine collected from male rats.9. The M1, M2 metabolites and intact drug were also found in the 0-24hr fractions of bile in male rats.