Kitasato I, Niizato T, Watanabe T, Inouye S
Research & Development, Meiji Seika Kaisha Ltd., Tokyo, Japan.
Drugs Exp Clin Res. 1989;15(6-7):239-47.
Seven N-alkylsulfonate derivatives of an aminoglycoside antibiotic, dibekacin, were prepared and their nephrotoxicity was examined. Using water-supplied and water-depleted rats and the BUN value as a nephrotoxic measure, dibekacin-di-N-methanesulfonate, pentasodium dibekacin-penta-N-methanesulfonate, -penta-N-ethanesulfonate, disodium dibekacin-di-N-methanesulfonate sesquisulfate, disodium and dipotassium dibekacin-di-N-ethanesulfonate sesquisulfates and sodium dibekacin-mono-N-ethane-sulfonate disulfate showed low nephrotoxicity as compared to that of the original dibekacin sulfate. Notably, dibekacin-di-N-methanesulfonate caused little change in the BUN value and was bioactive in vitro but not active in vivo against a Pseudomonas aeruginosa infection model in mice. Among the bioactive N-alkylsulfonates in vivo, disodium and dipotassium dibekacin-di-N-ethanesulfonate sesquisulfates showed a lower degree of elevation of BUN, urine volume and urine protein, lower mortality and better body weight gain than those of dibekacin sulfate during consecutive treatment for 12 and 28 days.
制备了氨基糖苷类抗生素地贝卡星的七种N - 烷基磺酸盐衍生物，并检测了它们的肾毒性。以给水和缺水大鼠以及血尿素氮（BUN）值作为肾毒性指标，与原始硫酸地贝卡星相比，地贝卡星二 - N - 甲磺酸盐、地贝卡星五钠 - 五 - N - 甲磺酸盐、 - 五 - N - 乙磺酸盐、地贝卡星二 - N - 甲磺酸盐倍半硫酸盐二钠、地贝卡星二 - N - 乙磺酸盐倍半硫酸盐二钠和二钾以及地贝卡星 - 单 - N - 乙磺酸盐二硫酸盐显示出较低的肾毒性。值得注意的是，地贝卡星二 - N - 甲磺酸盐使BUN值变化很小，在体外具有生物活性，但在体内对小鼠铜绿假单胞菌感染模型无活性。在体内具有生物活性的N - 烷基磺酸盐中，地贝卡星二 - N - 乙磺酸盐倍半硫酸盐二钠和二钾在连续治疗12天和28天期间，与硫酸地贝卡星相比，血尿素氮、尿量和尿蛋白的升高程度较低，死亡率较低，体重增加较好。
