Synthesis, in vivo effects, metabolism, and excretion of 5 (p hydroxyanilino) 1,2,3,4 thiatriazole in the beagle dog

Article abstract of DOI:10.1021/jm00256a011

Trained normal and hypertensive beagle dogs were given tritiated 5 (p hydroxyanilino) 1,2,3,4 thiatriazole orally (30 mg/kg) and intravenously (20 mg/kg). Pasma levels of radioactivity as well as blood pressure and heart rate were measured concomitantly at various times following drug administration. The maximum hypotensive effect occurred 2 hr after intravenous administration and 4 to 8 hr after oral administration. This maximum effect did not correlate with maximum plasma levels of parent drug or metabolic, suggesting that a single agent may not be responsible for the hypotensive effect; a secondary mechanism may be involved. Excretion of radioactivity was followed for 5 to 6 days after administration. Biliary secretion of parent drug or its metabolites was indicated when 9 to 17% of intravenously administered drug radioactivity was excreted via the feces. Examination of urinary metabolites from each dog showed unchanged parent drug 5.7 to 20.7% (iv), 18.6 to 20.2% (oral); p aminophenol 45.9 to 66.5% (iv), 40.7 to 45.5% (oral). Urine from one dog was examined for other metabolites, and the following were found: p hydroxyphenylthiourea, 3.2 to 5.6%; p hydroxyphenylurea, 7.1 to 10.5%; APAP, 1.5 to 1.8%; unknown metabolite, 16.2 to 23.9%.