oxypurinol and orotidine

1. A compound identified as orotidine has been found in the erythrocytes of all subjects on allopurinol. 2. The erythrocyte orotidine concentrations were much higher in patients with renal failure or with the Lesch-Nyhan syndrome. 3. In addition, increased amounts of oxypurinol-7-riboside were excreted in the urine by both of these groups compared with control subjects or with patients with normal renal function on allopurinol. 4. A good correlation was found between urinary oxypurinol-7-riboside excretion and erythrocyte orotidine concentrations. 5. Increased erythrocyte levels of the pyrimidine-sugar UDP-glucose were also found in patients with the highest orotidine levels. 6. The combined results suggest a derangement of pyrimidine nucleotide metabolism during allopurinol therapy. We propose that erythrocyte orotidine formation results primarily from inhibition of orotidine-5'-monophosphate decarboxylase by oxypurinol-7-ribotide.

Topics: Allopurinol; Erythrocytes; Female; Humans; Kidney Failure, Chronic; Lesch-Nyhan Syndrome; Male; Nucleotides; Oxypurinol; Ribonucleosides; Uridine

We used a reversed-phase "high-performance" liquid-chromatographic system equipped with a multichannel ultraviolet spectrometric detector and a micro-computer for analyzing urine samples from patients with disorders of purine metabolism. This system recorded a series of absorption-spectrum data from a single chromatographic run and stored them for subsequent analysis. Because the retention times and ultraviolet absorption spectra of the eluates were recorded simultaneously, identification of peaks was easy and quite accurate for simultaneous quantification of orotidine, adenine, hypoxanthine, uric acid, xanthine, allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine), oxypurinol (4,6-dihydroxypyrazolo[3,4-d]pyrimidine), inosine, and 2,8-dihydroxyadenine--compounds extremely difficult or even impossible to quantify simultaneously with a conventional single-wavelength spectrometer. We used this method to investigate purine metabolites in urines from a patient with hereditary xanthinuria, three patients with 2,8-dihydroxyadenine urolithiasis, and a gouty subject taking allopurinol.

Topics: Adenine; Allopurinol; Chromatography, High Pressure Liquid; Humans; Hypoxanthine; Hypoxanthines; Inosine; Oxypurinol; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Spectrophotometry, Ultraviolet; Uric Acid; Uridine; Xanthine; Xanthines