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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
Author(s) -
Yamada Harumi,
Kotaki Hajime,
Furitsu Hisao,
Sawada Yasufumi,
Iga Tatsuji
Publication year - 1999
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199903)20:2<77::aid-bdd154>3.0.co;2-d
Subject(s) - uricosuric , hyperuricemia , uric acid , mechanism of action , medicine , drug , endocrinology , excretion , pharmacology , gout , chemistry , kidney , oral administration , biochemistry , in vitro
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 (FE urate ), 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 FE urate by E3040 was dose‐dependent. Although the FE urate 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≈2). Copyright © 1999 John Wiley & Sons, Ltd.