Disease relevance of Oxonic Acid

• Hyperuricemia and uricosuria were induced in rats fed uric acid and oxonic acid [1].
• Recent studies have reported that mild hyperuricemia in normal rats induced by the uricase inhibitor, oxonic acid (OA), results in hypertension, intrarenal vascular disease, and renal injury [2].
• Mean duration of ventricular fibrillation appeared to be reduced in hearts treated with 10(-3) and 10(-4) M oxonic acid compared to controls but these data did not achieve a level of statistical significance [3].
• Because oxonic acid is included to protect against gastrointestinal toxicity, this observation might affect the gastrointestinal toxicity and thus the efficacy of S-1 [4].
• There was no difference in the incidence of ventricular fibrillation or ventricular tachycardia in either uric acid or oxonic acid treated hearts compared to untreated controls [3].

High impact information on Oxonic Acid

• This selective inhibition of 5-FU phosphorylation in the GI tract was due to the much higher concentrations of oxonic acid in GI tissues than in other tissues and the blood [5].
• CONCLUSIONS: Food intake affected only the pharmacokinetics of the S-1 constituent oxonic acid but not of FT, CDHP, and 5FU [4].
• PURPOSE: The purpose is to determine the effect of food on the bioavailability of S-1, an oral formulation of the 5-fluorouracil (5FU) prodrug Ftorafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), a dihydropyrimidine dehydrogenase inhibitor, and oxonic acid (an inhibitor of 5FU phosphoribosylation in normal gut mucosa) in a molar ratio of 1:0.4:1 [4].
• The food/fast ratio for the AUC of FT was not different, which for 5FU was 0.84 (P = 0.041), for CDHP was 0.89 (P = 0.191), for oxonic acid was 0.48 (P < 0.0005), and for cyanuric acid, the breakdown product of oxonic acid, was 5.1 (P = 0.019) [4].
• PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities(DLTs), and pharmacokinetics of S-1, a combination of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and oxonic acid, administered once daily in patients with advanced cancer [6].

Chemical compound and disease context of Oxonic Acid

• Allopurinol prevented hyperuricemia (1.14 +/- 0.2 mg/dl), systemic (121.8 +/- 2.8 mmHg) and glomerular hypertension (50.1 +/- 0.8 mmHg), and arteriolopathy in oxonic acid-treated rats [7].
• S-1 (TS-1), a combination of ftorafur and two modulators, gimestat (CDHP) and oxonic acid, in a molar ratio of 1:0.4:1, has been widely used in Japan for the treatment of advanced gastric cancer, and much attention has been paid to attempts to increase its antitumor effect by combining it with other chemotherapeutic drugs [8].

Biological context of Oxonic Acid

• Rats fed 2% oxonic acid and a low-salt diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05), hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and afferent arteriolar thickening, with a 35% increase in medial area (P < 0.05) [9].
• Pharmacokinetics of S-1, an oral formulation of ftorafur, oxonic acid and 5-chloro-2,4-dihydroxypyridine (molar ratio 1:0.4:1) in patients with solid tumors [10].
• Oxonic acid and fetal development: I. Embryotoxicity in mice [11].

Anatomical context of Oxonic Acid

• This oxidation is ascribed to a copper-stimulated, membrane-associated uricase since purified uricase and the membranes had similar Km values, both were inhibited by oxonic acid, and extramembranal uricase was not detected [12].

Associations of Oxonic Acid with other chemical compounds

• MATERIALS AND METHODS: A model of acute uric acid nephropathy was induced in rats by the administration of oxonic acid (an inhibitor of uricase), together with uric acid supplements [13].
• High-resolution X-ray structures of the complexes of Aspergillus flavus urate oxidase (Uox) with three inhibitors, 8-azaxanthin (AZA), 9-methyl uric acid (MUA) and oxonic acid (OXC), were determined in an orthorhombic space group (I222) [14].
• Blood pressure could also be lowered by reducing uric acid levels with either allopurinol or oxonic acid withdrawal [15].

Gene context of Oxonic Acid

• Urate-oxidase in liver of oxonic acid treated mice [16].
• Oxonic acid is not an ideal uricase inhibitor, because it is competitive and is eliminated from the body relatively rapidly [17].

Analytical, diagnostic and therapeutic context of Oxonic Acid

• Control groups included rats treated with vehicle (VEH) and oxonic acid alone (OA) [18].
• Following a single intraperitoneal injection of oxonic acid, urate-oxidase inhibitor with optical and chromatographic properties of the injected drug was found in the supernatants of mouse liver homogenates [16].

References