INHIBITION OF UREASE BY MISCELLANEOUS IONS AND COMPOUNDS - IMPLICATIONS FOR THERAPY OF INFECTION-INDUCED UROLITHIASIS

Abstract

One hundred forty-eight drugs and other organic and inorganic substances were screened for their ability to inhibit enzyme urease in an in vitro system modeled on infected urine. Reported urease-inhibiting properties of ascorbic acid, tetracyclines and sulfanilamide were not confirmed. At least 50% inhibition was observed in presence of kanamycin, hydroxyguanidine, benzoquinone, 1,2-naphthaquinone-4-sulfonate, chloramine-T, N-bromoacetamide, Cu, Hg and fluoride. It is unlikely that therapeutically effective concentrations can be attained in urine without giving dosages likely to result in toxic effects. Hydroxyurea, at the dose level used in cytotoxic therapy, may be expected to produce effective inhibition of bacterial urease in the urinary tract, providing renal function is unimpaired and providing urinary volume does not exceed 1 l/24 h. Acetohydroxamic acid is potentially the most useful drug for treatment of infection-induced urinary stone disease.