Mechanism of the uricosuric action of the anti-inflammatory drug E3040 used to treat inflammatory bowel disease I: Study using a rat model of hyperuricemia

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 stu dy, 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 significantl y elevated as compared with that in the control. This elevation of the FEur ate by E3040 was dose-dependent. Although the FEurate was elevated spontane ously 30 min after administration of E3040-sulfate (E-Sul) and glucuronide (E-Glu) (100 mg kg(-1), respectively), the value was not significantly diff erent from the control. Based on these results, it was suggested that E3040 has a uricosuric action, probably in the proximal tubules, and the uricosu ric action after administration of E3040 may be mainly due to the parent dr ug. Concerning the tissue distribution, the kidney concentration of E-Sul a fter i.v. administration of the E3040 (50 mg kg(-1)) was higher than that o f the parent drug (kidney/plasma ratio approximate to 2). Copyright (C) 199 9 John Wiley & Sons, Ltd.