The absorption, distribution, and excretion of 3-trifluoremethyl-s-triazolo(3,4-α)isoquinoline

Abstract The absorption, distribution, and excretion of 3-trifluoromethyl- s -triazolo (3,4-α)isoquinoline (NC-1140) was studied in the dog, rat, and monkey. Employing a spectrophotofluorometric assay, maximum drug levels in serum were attained at 2 hr in the dog and 3 hr in the monkey, and an elevated “plateau” was observed in the rat from 1 to 8 hr after dosing. Distribution studies on animals dosed orally with the 14 C-NC-1140 indicate that liver and skeletal muscle accounted for as much as 30% of the administered radioactivity to 8 hr after dosing in all 3 species. In dogs and rats, relatively stable levels of radioactivity persisted in the gastrointestinal tract to 24 hr post administration. The dog excreted 60% of the po administered radioactivity in urine and feces within 24 hr and 97% within 48 hr. With urine accounting for approximately 60% and feces 40% of the total, a biological half-life of 21 hr in the dog was obtained. The rat excreted 55% of the radioactivity in 24 hr and 75% in 48 hr. Over a 72-hr sampling period, the urine accounted for 75% of the total and feces, 18%. The biological half-life in the rat was found to be 19 hr. The biliary excretion of 14 C-NC-1140 was determined in animals dosed po or iv. In animals dosed po, 23.8% of the radioactivity was recovered in dog bile over an 8-hr period, 2.5% in monkey bile during the same length of time, and 12.9% in rat bile within a 6-hr period. When the drug was administered iv, 50% of the radioactivity was recovered in dog and rat bile within 4 hr, but only 5.5% in monkey bile during the same length of time.