E3040, a new class of anti-inflammatory
drug, was found to reduce the plasma
uric acid level in the first phase of clinical studies. In the present study, the mechanism of the uricosuric action of
E3040 was investigated using the
hyperuricemia model rat. The fractional excretion of
uric acid (FEurate), an
indicator of the excretion of
uric acid in the renal tubules, at 30, 60 and 90 min after administration of
E3040 (50 mg kg(-1)) was significantly elevated as compared with that in the control. This elevation of the FEurate by
E3040 was dose-dependent. Although the FEurate was elevated spontaneously 30 min after administration of E3040-sulfate (E-Sul) and
glucuronide (
E-Glu) (100 mg kg(-1), respectively), the value was not significantly different from the control. Based on these results, it was suggested that
E3040 has a uricosuric action, probably in the proximal tubules, and the uricosuric action after administration of
E3040 may be mainly due to the parent
drug. Concerning the tissue distribution, the kidney concentration of E-Sul after i.v. administration of the
E3040 (50 mg kg(-1)) was higher than that of the parent
drug (kidney/plasma ratio approximately 2).