Metabolism of 1-(3-Trifluoromethylphenyl)- 3-(2-hydroxyethyl) quinazoline-2,4(1H,3H)-dione(H-88): I. Species Differences in Metabolism

Abstract

1. Following oral administration of [¹⁴C]H-88 to rat, mouse, guinea-pig and hamster, 40-65% and 5-15% of radioactivity was excreted in urine and faeces respectively during 3 or 4 days. In rabbit, monkey and man, more than 80% of radioactivity was excreted in urine during 2 or 3 days, and faecal excretion was negligible.

2. Rabbit, rat or guinea-pig excreted non-labelled H-88 in urine as unchanged H-88 (M-I), 1-(3-trifluoromethylphenyl) quinazoline-2,4(1H,3H)-dione-3-acetic acid (M-I I), H-88 glucuronide (M-III) and 1-(3-trifluoromethylphenyl)- 3-(2-hydroxyethyl)-6-hydroxyquinazoline-2,4(1H,3H)-dione (M-IV).

3. The carboxylic acid (M-II) was the major metabolite of H-88 in rat, mouse, guinea-pig and hamster urine and faeces, while the major metabolite in urine of rabbit, monkey and man was H-88 glucuronide (M-III). The 6-hydrexy compound (M-IV) was a major metabolite only in guinea-pig.