Evaluation of effects of novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid on the formation of an infection bladder stone using a newly designed urolithiasis model in rats.
By using our new infection stone model of a rat, we evaluated the effect of a novel urease inhibitor, N-(pivaloyl)glycinohydroxamic acid (P-GHA), on the formation of an infection bladder stone. The oral dosing of P-GHA significantly inhibited the elevation of the urinary ammonia level of rats having the urinary tract infection with Proteus mirabilis. A short term regimen (7 d, 730 +/- 38 mg/kg) with P-GHA significantly inhibited the development of the infection bladder stone. Furthermore, a long term combination regimen (11 d) of P-GHA and aminobenzylpenicillin markedly inhibited the development of the infection bladder stone, and also caused a very slight renal impairment to the rats tested in contrast with the method of Vermeulen et al. Our infection stone model in rats, therefore, seems to be useful for the evaluation of therapeutic agents in long term examinations.
Satoh
M
M
Eisai Research Laboratories, Tokyo, Japan.
Munakata
K
K
Takeuchi
H
H
Yoshida
O
O
Takebe
S
S
Kobashi
K
K
D000667:Ampicillin / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014510:Urease / Q000037:antagonists & inhibitors*; D001744:Urinary Bladder Calculi / Q000517:prevention & control*; D014552:Urinary Tract Infections / Q000517:prevention & control*
D006877:Hydroxamic Acids; C032346:N-(pivaloyl)glycinohydroxamic acid; D000667:Ampicillin; D014510:Urease