Metabolism of 1-(3-Trifluoromethylphenyl)-3-(2-hydroxyethyl)quinazoline-2,4(1H,3H)-dione (H-88). II. Absorption, Distribution and Excretion in Rat, Mouse, Rabbit, Monkey and Man

Abstract

1. The maximum concentration of radioactivity in blood occurred 2-4 h after oral administration of [¹⁴C]H-88 in mouse, rabbit and man. With rat, a maximum concentration was obtained 24 h after administration of the drug at a dose level of 60 mg/kg, but only 4 h at a dose of 6 mg/kg. Unchanged H-88 comprised about 50% of serum radioactivity in rat and mouse during the first few hours, but only a small proportion of the serum radioactivity in rabbit and man.

2. The distribution pattern of the radioactivity in rat given the drug at two dose levels was similar, and this differed slightly from mouse and considerably from rabbit. Autoradiograms in rat and rabbit confirmed the findings from the distribution studies, and the autoradiographic distribution pattern in monkey was similar to that in rabbit.

3. Of the administered radioactivity 25-30% was recovered from bile within 48 h in bile-duct-cannulated rats and rabbits. Excretion of radioactivity in respiratory CO₂ was negligible in the rat.