Studies on the Metabolic Fate of Nizatidine (II) Transfer into the Fetus and Milk, and Absorption, Distribution, Metabolism and Excretion after Repeated Administration to Rats.

Abstract

Transfer of ¹⁴C-nizatidine into the fetus and milk after oral administration to pregnant or lactating rats, and the absorption, distribution, metabolism and excretion of ¹⁴C-nizatidine after repeated administration to male rats were studied.
1. On day 13 and 18 of gestation, the radioactivity in the fetus was lower than that in the maternal blood based on autoradiography. On day 18 of gestation, the radioactivity levels in the fetal liver and kidney were higer than that in the maternal plasma, but at 48 hr after oral administration the radioactivity levels decreased to 5 % and 2 % of the highest concentration, respectively.
2. The concentrations of radioactivity in the milk were higher than that in the maternal plasma until 6 hr after administration, however the disappearance of radioactivity from the milk was significantly faster and was not detected at 48 hr after administration.
3. In the study with repeated administration, blood levels of radioactivity until 24 hr reached the steady state after the 14 th dose. Cumulative excretion ratios with urine and feces were constant after the 3rd administration. The concentrations of radioactivity in the tissues at 24 hr reached the steady state after the 14th dose, but the disappearance of radioactivity from tissues after the 21 th dose was relatively slow.
4. In the plasma and urine after the 21 th dose, the unchanged drug, N-desmethyl and S-oxide metabolites were detected as major component and M-3 and M-5 were also detected in the urine, however at low concentrations.