Hypouricemic effect of allopurinol and the novel xanthine oxidase inhibitor TEI-6720 in chimpanzees.
The hypouricemic effect of a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid, was investigated and compared with that of allopurinol in male chimpanzees (n = 3). When allopurinol (10 mg/kg) was administered orally once a day for three consecutive days, it cumulatively reduced serum urate levels by 29.7, 50.1 and 60.2%, 24, 48 and 72 h, respectively, after the initial dose. This effect was dose dependent at doses of 3 and 10 mg/kg. At 3 mg/kg, the mean serum urate levels were 3.1, 2.4, 2.5 and 2.3 mg/dl before and 24, 48 and 72 h, respectively, after the initial dose. Animals treated with 10 mg/kg of allopurinol showed serum urate levels of 3.3, 2.3, 1.6 and 1.3 mg/dl, respectively. The urate-lowering effect of TEI-6720 was then compared with that of allopurinol at a daily dose of 5 mg/kg (n = 3). Both compounds caused striking reductions in serum and urinary uric acid levels accompanied by an increase in urinary xanthine levels. These effects of TEI-6720 were more potent than those of allopurinol. TEI-6720 reduced serum urate levels by 55.9, 69.6 and 73.6%, 24, 48 and 72 h, respectively, after the first dose, whereas the corresponding values after allopurinol were 28.1, 41.6 and 45.1%. These results suggest that the hypouricemic effect of TEI-6720 may be more potent than that of allopurinol in the treatment of hyperuricemia and gout, and that TEI-6720 may become an effective alternative drug.
Komoriya
K
K
Teijin Institute for Bio-medical Research, Tokyo, Japan.
Osada
Y
Y
Hasegawa
M
M
Horiuchi
H
H
Kondo
S
S
Couch
R C
RC
Griffin
T B
TB
D000284:Administration, Oral; D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000069465:Febuxostat; D005260:Female; D006073:Gout / Q000188:drug therapy; D008253:Macaca mulatta; D008297:Male; D002679:Pan troglodytes; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014527:Uric Acid / Q000097:blood* / Q000652:urine; D019820:Xanthine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*; D014970:Xanthines / Q000097:blood / Q000652:urine
D013844:Thiazoles; D014970:Xanthines; D000069465:Febuxostat; D019820:Xanthine; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase