title: Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol "Preliminary Communication".
abstract: The effects of tofisopam, a GABA-receptor agonist, following oral administration (300mg) with and without allopurinol pretreatment on the plasma concentration and renal transport of uric acid and oxypurinol were investigated in 5 healthy subjects. Fractional and urinary excretions of uric acid were both significantly increased at 2-3 hours after tofisopam administration (559% and 459%, respectively), while plasma uric acid concentration was significantly decreased (36%) at 2.5 hours, suggesting that tofisopam affects uric acid metabolism via the tubular transport system. The hypouricemic effect of tofisopam was comparable to or greater than that of losartan and/or fenofibrate, which also have uric acid-lowering activity. In addition, with prior administration of allopurinol, the fractional and urinary excretions of oxypurinol were increased at 2-3 hours after tofisopam administration (51% and 33%, respectively), while the plasma oxypurinol concentration was significantly decreased at 1.5 and 2.5 hours (15% and 21%, respectively). Accordingly, tofisopam may be an attractive compound for treatment of hyperuricemia and/or gout, especially in patients complicated with autonomic dysfunction symptoms, though it is possible that the uric acid-lowering effect of oxypurinol is attenuated by tofisopam.
authors.forename: Miki
authors.initials: M
authors.lastname: Hatayama
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sumida
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurajoh
authors.forename: Jun
authors.initials: J
authors.lastname: Shiraishi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okazaki
authors.forename: Takuhito
authors.initials: T
authors.lastname: Shoji
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.forename: Zenta
authors.initials: Z
authors.lastname: Tsutsumi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Moriwaki
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Namba
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
keywords: Allopurinol; hyperuricemia; levotofisopam; renal transport; uricosurics