Disease relevance of Oxonic Acid

• PURPOSE: Our purpose in the study was to determine the maximum tolerated dose and dose-limiting toxicity and investigate the clinical pharmacology of S-1, a combination of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate [1].
• Oxonate-induced hyperuricemia and orotic aciduria in mice [2].
• Adjuvant polyarthritis. VI. Effect of oxonate-induced hyperuricemia on the development of acute inflammation, immune response and adjuvant arthritis [3].
• We conducted a phase II trial of gemcitabine with S-1, oral fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate, to evaluate the activity and toxicity of such a combination in metastatic pancreatic cancer (MPC) patients [4].
• Therapeutic effect of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) on liver metastasis of xenotransplanted human colon carcinoma [5].

High impact information on Oxonic Acid

• PURPOSE: To investigate the side effects, determine the maximum-tolerated dose (MTD), and study the pharmacokinetics of S-1, an oral fluoropyrimidine-based antineoplastic agent consisting of the fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium oxonate [6].
• S-1 is a combination of tegafur (FT), 5-chloro-2,4-hydroxypyridine, and potassium oxonate in the molar ratio of 1.0:0.4:1.0, with the latter two components as inhibitors of dihydropyrimidine dehydrogenase and phosphoribosylpyrophosphate transferase, respectively [7].
• A similar time-lag was observed between the lowering of the hyperuricaemia and the reduction of platelet aggregation when oxonate was removed from the diet [8].
• OBJECTIVE: S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase, and potassium oxonate (Oxo), a reducer of gastrointestinal toxicity [9].
• However, unlike that of normal animals, the cell-mediated immune system of the oxonate-treated rats was found to be unable to respond to adjuvant stimulation, which may be the basis for their resistance to develop adjuvant disease [3].

Chemical compound and disease context of Oxonic Acid

• 5-FU therapy often causes gastrointestinal toxicity, which is suppressed by concomitant administration of potassium oxonate (Oxo) [10].
• We evaluated the hypouricemic effect of TEI-6720 on hyperuricemia induced by the uricase inhibitor, potassium oxonate (250 mg/kg s.c., 1 h before the test drugs), and measured the total molarity of both serum allantoin and urate in rats [11].
• The natural product aesculin was demonstrated to possess potent hypouricemic effects in in vivo models of hyperuricemia in both mice and rats pretreated with oxonate [12].
• Thus, we concluded that allantoxanamide might be a useful reagent for investigating the causes of hyperuricemia with renal failure, but was not a practical agent like oxonate in order to evaluate the response to uricosuric agents [13].
• In oxonate-treated rats, probenecid was hyperuricosuric, increasing the glomerular-filtered amounts of uric acid and causing marked hyperuricemia [14].

Biological context of Oxonic Acid

• Tissue distribution and biotransformation of potassium oxonate after oral administration of a novel antitumor agent (drug combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate) to rats [15].
• Feeding the uricase inhibitor potassium oxonate (KOx) as 3% of the diet to pregnant rats beginning on the 8th day of gestation for either 2 or 3 days caused a time-related increase in fetal resorptions, with the incidence in the experimental group treated for the additional day being 72% higher than the 2-day group [16].

Anatomical context of Oxonic Acid

• Oxonate loading was performed by continuous infusion into the femoral vein [17].
• Treatment with FT and CDHP (groups B and C) induced injury to the small intestine and decreased expression of CD44 within the intestinal mucosa, but the extent of damage was reduced by coadministration of Oxo (group C) [18].

Associations of Oxonic Acid with other chemical compounds

• The methanol extract from the leaves of PHYLLANTHUS NIRURI L. showed oral antihyperuricemic activity in potassium oxonate- and uric acid-induced hyperuricemic rats [19].
• MATERIALS AND METHODS: In a retrospective study, 41 patients with GC treated with paclitaxel alone (n=12) or a combination of docetaxel and S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine, potassium oxonate) (n=29) were studied [20].
• The enzyme had a pH optimum of 9.0, a K(m) of 35 microM for urate, and it was inhibited only by oxonate and xanthine [21].
• Both potassium oxonate and allantoxanamide have been reported as useful reagents for inhibiting urate oxidase, with the hyperuricemic effect of allantoxanamide being longer-lasting than that of oxonate in rats [13].
• The effects of the continuous intravenous infusion of diltiazem on plasma urate levels and the urinary excretion of urate were examined in urethane anesthetized oxonate-loaded rats [22].

Gene context of Oxonic Acid

• Platelet aggregation in rats made hyperuricaemic with nucleic adid-rich diets containing oxonate, and inhibitor of uricase [proceedings] [23].
• Reduction of 5-fluorouracil (5-FU) gastrointestinal (GI) toxicity resulting from the protection of thymidylate synthase (TS) in GI tissue by repeated simultaneous administration of potassium oxonate (Oxo) in rats [24].
• Feeding the uricase inhibitor potassium oxonate (K Ox) as 3( of the diet to pregnant mice during days 8-10 postconception caused a 95-98% incidence of embryonic mortality with resorption [25].
• We investigated the hypouricemic effects of cassia oil extracted from Cinnamomum cassia using hyperuricemic mice induced by potassium oxonate, and its inhibitory actions against liver xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) activities [26].

Analytical, diagnostic and therapeutic context of Oxonic Acid

• Similarly, rats rendered hyperuricemic by an oxonate diet appeared resistant to develop adjuvant arthritis [3].
• Nephrectomy markedly potentiated cholinergic agent-induced hyperuricemia, and methylatropine but not hexamethonium apparently abolished the induction of hyperuricemia both in potassium oxonate-treated rats and in eviscerated rats with nonfunctioning livers and without kidneys [27].
• The oxonate-treated rat can serve as a useful animal model not only in investigation of the uric acid nephropathy, but also in a number of other toxicologic evaluations connected with uric acid [28].
• Determination of S-1 (combined drug of tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate) and 5-fluorouracil in human plasma and urine using high-performance liquid chromatography and gas chromatography-negative ion chemical ionization mass spectrometry [29].

References