Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol “Preliminary Communication”

Title:Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol “Preliminary Communication”

Volume: 10 Issue: 2

Author(s): Miki Hatayama, Chihiro Sumida, Masafumi Kurajoh, Jun Shiraishi, Hirokazu Okazaki, Takuhito Shoji, Hidenori Koyama, Zenta Tsutsumi, Yuji Moriwaki, Mitsuyoshi Namba and Tetsuya Yamamoto

Affiliation:

Keywords: Allopurinol, hyperuricemia, levotofisopam, renal transport, uricosurics

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.

Cite this article as:

Hatayama Miki, Sumida Chihiro, Kurajoh Masafumi, Shiraishi Jun, Okazaki Hirokazu, Shoji Takuhito, Koyama Hidenori, Tsutsumi Zenta, Moriwaki Yuji, Namba Mitsuyoshi and Yamamoto Tetsuya, Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of Uric Acid and Oxypurinol “Preliminary Communication”, Current Clinical Pharmacology 2015; 10 (2) . https://dx.doi.org/10.2174/1574884710666150126143421