Pharmacokinetics/pharmacodynamics of Y-700, a novel xanthine oxidase inhibitor, in rats and man.

Abstract

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.

• Authors: I Yamada, A Fukunari, T Osajima, M Kamezawa, H Mori, J Iwane
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 23 Issue 8-9 Pg. 1123-5 (Oct 2004) ISSN: 1525-7770 [Print] United States
• PMID: 15571214 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid
• Enzyme Inhibitors
• Pyrazoles
• Uric Acid
• Xanthine Oxidase

Topics

• Administration, Oral
• Adult
• Animals
• Area Under Curve
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Humans
• Hyperuricemia (drug therapy)
• Male
• Pyrazoles (pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Uric Acid (blood)
• Xanthine Oxidase (antagonists & inhibitors)