Pharmacokinetic and pharmacodynamic properties of a novel xanthine oxidase inhibitor, BOF-4272, in healthy volunteers.


A novel pyrazolotriazine derivative [BOF-4272, sodium-(+-)-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo[1,5-a]-1 ,3,5-triazine-4-olate monohydrate], which inhibits biosynthesis of uric acid (UA) by interfering with xanthine oxidase/xanthine dehydrogenase, was administered p.o. to healthy male volunteers to evaluate its pharmacokinetic and pharmacodynamic properties. In the single-dose study, three doses of BOF-4272 (100, 200 and 400 mg) and a placebo were allocated to eight subjects on three occasions at more than 1-week intervals in a single-blind and balanced incomplete block design. In the multiple-dose study, 200 mg of BOF-4272 and a placebo were administered to six and four subjects, respectively, twice daily for 6.5 days (13 total doses) in a single-blind design. Throughout the whole study period BOF-4272 was well tolerated in healthy subjects. In the single-dose study, the maximal plasma concentrations of BOF-4272 and its major metabolite (M-4) and their areas under the plasma concentration-time curve increased in proportion to the given dose. Both substances were eliminated from plasma with half-lives of 1.7 to 1.9 and 4.8 to 6.9 hr irrespective of the dose. BOF-4272 was recovered in the urine at about 1% as unchanged drug and 15% as M-4. In the single-dose study, serum UA concentration was decreased dose-dependently to about 80% of the predose value. In the multiple-dose study, serum UA concentration, which was measured before each morning dose, was decreased to about 72% on day 3 and maintained thereafter at almost the same level until 24 hr after the last administration.(ABSTRACT TRUNCATED AT 250 WORDS)


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@article{Uematsu1994PharmacokineticAP, title={Pharmacokinetic and pharmacodynamic properties of a novel xanthine oxidase inhibitor, BOF-4272, in healthy volunteers.}, author={Toshihiko Uematsu and Mihoko N. Nakashima}, journal={The Journal of pharmacology and experimental therapeutics}, year={1994}, volume={270 2}, pages={453-9} }