ウレアーゼ阻害剤による尿路結石の予防 第2報: ヒドロキサム酸の尿中排泄とラット膀胱結石の形成防止効果

Abstract

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.