Pharmacologic evaluation of the renal handling of uric acid and oxypurines.
The effect of drugs that alter the renal tubular transport of urate in the renal excretion of the oxypurines, hypoxanthine (Hx) and xanthine (X), was used to analyze the tubular mechanisms involved in oxypurine excretion in normal subjects and in patients with idiopathic renal hypouricemia. In healthy subjects, administration of the drugs, benzbromarone (Bb) and probenecid (Pb), brought a marked uricosuric effect, but did not alter oxypurine excretion. One of 2 hypouricemic patients exhibited no uricosuric effects with Bb and the other showed a slight uricosuric effect with the drug. Bb administration, however, produced no increase in oxypurine excretion in either patient. In healthy subjects, administration of pyrazinamide (PZA) suppressed the excretion of urate and oxypurines to varying degrees: relative to the baseline values, the fraction excretion of urate was reduced by 95% or more, that of Hx by about 24%, and that of X by about 64%. In patients with hypouricemia, the effects of PZA on urate and oxypurine excretion were impaired. According to these findings, we can speculate that the oxypurines have the same renal secretory mechanism as uric acid. However, the reabsorptive mechanisms of oxypurines at the postsecretory site are likely to differ from that of uric acid.
2nd Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Kitakyushu city, Fukuoka, Japan.
K
K
Hiroshige
M
M
Takasugi
K
K
Yuu
A
A
Kuroiwa
D000328:Adult; D001553:Benzbromarone / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D011339:Probenecid / Q000494:pharmacology*; D011718:Pyrazinamide / Q000494:pharmacology*; D014527:Uric Acid / Q000378:metabolism*; D014970:Xanthines / Q000378:metabolism*
D007042:Hypoxanthines; D014970:Xanthines; D014527:Uric Acid; D011718:Pyrazinamide; D019271:Hypoxanthine; D001553:Benzbromarone; D011339:Probenecid