PREVENTION OF INFECTED URINARY STONES BY UREASE INHIBITOR 2.URINARY EXCRETION OF HYDROXAMIC ACIDS AND PREVENTION OF INFECTED BLADDER STONES IN RATS

摘要

Phosphatic stones, particularly struvite stones, are thought to develop in the urinary tract infected by urea splitting microorganism. The hydroxamic acid is known to be a specific and effective inhibitor of bacterial urease. Urinary excretion of several hydroxamic acid derivertives was investigated after oral administration to the experimental rats. Approximately 30% of acetohydroxamic acid was excreted in urine unchanged for 24 hours after administration. 24 hour excretions of other hydroxamic acids were as follows: serine-9%, histidine-3.4%, nicotino-1.0%, caplyro-1.0%, glycine-0.9% and benzo-0.6%. Effective index (=recovery % /I50 (µM)) of acetohydroxamic acid was 3.05 and that of nicotinohydroxamic acid was 0.50. Teratogenic action of acetohydroxamic acid in rats had been reported, but that of nicotinohydroxamic acid was not reported yet. Administration of nicotinohydroxamic acid to rats with urinary tract infection caused by Proteus mirabilis significantly prevented alkalinization of urine as well as bladder stone formation. The extent of pyelonephritis and azotemia was much less than that in the untreated control animals. The hydroxamic acid derivatives more potent than nicotinohydroxamic acid will become useful drugs for the prevention of struvite stones.