Studies on the Metabolic Fate of Azuletil Sodium (III) : Absorption, Distribution, Metabolism and Excretion after Repeated Oral Administration to Rats, Transfer into the Fetus and Milk, and Induction of the Liver Microsomal Drug-Metabolizing Enzymes by the Repeated Oral Administration to Rats.

Abstract

The absorption, distribution and excretion of ¹⁴C-KT1-32 were studied after repeated oral administration to male rats. Transfer of radioactivities into the fetus and milk after oral administration of ¹⁴C-KT1-32 to pregnant or lactating rats were studied. The induction of the hepatic drug-metabolizing enzymes was studied after repeated oral administration of KT1-32 to male rats.
1. On day 13 and 18 of gestation, the autoradiography revealed that the radioactivity in the fetus was lower than that in the maternal blood. On day18 of gestation, the radioactivities in the fetal liver and kidney were lower than that in the maternal plasma.
2. The radioactivity in the milk was lower than that in the maternal blood within 8hr after administration. The disappearance of radioactivity from the milk was slower than that from the blood.
3. After repeated administration, the radioactivity in the blood reached the steady state within 24hr following the 1st administration. Cumulative excretion ratios in urine and feces reached a constant value after the 3rd administration. The radioactivities in the tissues at 24 hr reached the steady state after the 7th administration, but the disappearance of radioactivity from the tissues after the 21st administration was quite similar to that after single administartion.
4. In the plasma and urine after the 21st administration, the Ml, M2 metabolites and the intact drug were detected as major components and M4, M3, M5 and M6 were found in the urine as the minor ones.
5. After repeated oral administration of KT1-32 to male rats, there was no induction of the hepatic drug-metabolizing enzymes.