Studies on the Metabolic Fate of Felodipine. (V): Absorption, Distribution, Metabolism and Excretion after a Single Oral Administration to Dogs.

Abstract

The absorption, distribution, metabolism and excretion of 14C-nizatidine were studied after a single oral or intravenous administration of 5 mg/kg to rats.1. The blood levels of radioactivity reached a maximum concentration at 30 min after oral administration, corresponding to 668 and 426 ng equivalent of nizatidine/ml, and then declined within the first 6 hr with half-lives of 1.43 and 1.38 hr in male and female rats, respectively. The half-lives in the ranges of 8-24 hr were 10.3 hr in male, and 15.4 hr in female.2. The blood level of radioactivity declined biexponentially with half life of 0.66 hr in the first 4 hr and 27.0 hr in the range between 6 hr and 48 hr after intravenous administration in male rats.3. Male rats excreted 68.0 % of the dose in urine and 27.1 % of the dose in feces until 120 hr after oral administration. Until 120 hr after intravenous administration, male rats excreted 84.2 and 16.2 % of the dose in urine and feces, respectively. The biliary excretion within 48 hr after oral administration was 20.2% of the dose in male rats, while the excretion of the radioactivity reabsorbed, as a percent of the dose, was 5.8% in bile and 30.3% in urine until 48 hr after intraduodenal injection.Female rats excreted 59.7 % of the dose in urine and 39.1 % of the dose in feces until 120 hr after oral administration.4. The radioactivity levels in the tissues except the testis reached a maximum concentration at 30 min after oral administration in male rats, and relatively high radioactivity was found the kidney, small intestine, liver, urinary bladder and stomach. The other tissues contained nearly the same concentrations of radioactivity as plasma, or somewhat lower. At 120 hr after oral administration, the radioactivity in most tissues was not detectable.5. The plasma protein binding in vitro was 12.8-16.9% at concentrations range between 0.1 and 10 μg/ml, and that in vivo was 20.6, 26.2 and 41.8% in the plasma sample collected 0.5, 2 and 6 hr after administration, respectively.6. In the fractions of plasma and urine collected in male and female rats after oral administration, the unchanged drug, N-desmethyl and S-oxide metabolites were the main components and the other minor compounds, M-3 and M-5, were also detected in the urine. In the fractions of bile in male rats, M-2, M-4, M-5 were detected with the unchanged drug, N-desmethyl and S-oxide metabolites.