Pharmacokinetics/pharmacodynamics of Y-700, a novel xanthine oxidase inhibitor, in rats and man.
The pharmacokinetics and pharmacodynamics of a novel xanthine oxidase (XO) inhibitor, Y-700, were evaluated in rats and healthy male volunteers. In a rat model of hyperuricemia, oral Y-700 (0.3-10 mg/kg) showed a more potent and a longer-lasting hypouricemic action than allopurinol. A single oral dosing of Y-700 (5, 20 or 80 mg) to volunteers caused a dose-dependent reduction of serum uric acid levels indicating close relationship to plasma concentrations of the compound. In addition, Y-700 was hardly excreted in urine but mainly excreted in feces in rats and volunteers. These results suggested that Y-700 is a new effective inhibitor of XO in rats and humans with high oral bioavailability being predominantly eliminated via the liver unlikely to allopurinol.
Yamada
I
I
Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, Kisarazu-shi, Chiba, Japan.
Fukunari
A
A
Osajima
T
T
Kamezawa
M
M
Mori
H
H
Iwane
J
J
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy; D008297:Male; D011720:Pyrazoles / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
C433950:1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D014527:Uric Acid; D014969:Xanthine Oxidase