Uric acid riboside

Figure 9.99 Separation of the components of the reaction studied (catalysis by nucleoside phosphorylase of a purine riboside-base conversion) by HPLC. Chromatographic conditions isocratic elution flow rate, 2 mL/min 0.02 F KH2P04 (pH 4.2) and 3% methanol. Peaks 1, uric acid 2, hypoxanthine 3, xanthine 4, inosine. (From Halfpenny and Brown, 1980.)...

Probenecid and benzbromarone increase the renal excretion of oxipurinol, the active metabolite of allopurinol, but this probably does not alter clinical efficacy. Theoretically, the use of uricosuric drugs with allopurinol could lead to uric acid precipitation in the kidneys and therefore maintenance of a high urine output is recommended when allopurinol is given by injection. Probenecid markedly increases the serum levels of allopurinol riboside, which may be advantageous in some circumstances. 

Allopurinol has been used for 16 years at doses ranging from 200 to 800 mg/day for the control of primary and secondary hyperuricemia. At the most commonly used doses of allopurinol (300-400 mg/ day) about 70% of the allopurinol is oxidized to oxipurinol, which is excreted in the urine. Urinary allopurinol and allopurinol riboside each account for about 10% of the dose. Since the degree of xanthine oxidase inhibition is dose-related, not only the oxidation of hypoxanthine and xanthine to uric acid, but also the oxidation of allopurinol to oxipurinol might be expected to be strongly inhibited at high doses of allopurinol. This would lead to increased levels of allopurinol, as well as allopurinol riboside, in plasma and urine. The extent to which this phenomenon occurs was investigated in several laboratory animal species and in man. 

Uric acid, hypoxanthine, xanthine, allopurinol, oxi-purinol and allopurinol-1-riboside by a modification of the method of Webster et al. on a Chrompack RP-8 column. Urine samples were preseparated on anion-exchange columns. For the determination of oxipurinol-7-riboside a preextraction of ribosides on Bio-Rad Affi-Gel 601 was necessary. For the determination of adenine the mobile phase contained 20% of methanol and was adjusted to pH 5.5. ... 

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