Bopp S, Marre R, Schulz E, Sack K
Arzneimittelforschung. 1981;31(3):473-7.
Nephrotoxicity, pharmacokinetics, and therapeutic efficacy of 3',4'-dideoxykanamycin (dibekacin), a semisynthetic aminoglycoside, were evaluated in rats. As with other aminoglycosides, therapy with dibekacin led to an increased urinary cell and malic-dehydrogenase excretion. The lowest dose resulting in an increased urinary cell excretion was 2.5 mg/kg/d. Serum levels of dibekacin after i.m. injection of 5 mg/kg were similar to those of other aminoglycosides. The kidneys accumulated high amounts of dibekacin, and eliminated it with a half-life of about 7 days. After repetitive dosing a distinct tendency to accumulation (highest renal concentration: 330 microgram/g) could be detected. Experimental chemotherapy of the chronic estrogen induced pyelonephritis revealed that dibekacin and sisomicin fed to significant reductions of renal bacterial counts at a dosage of 2 x 5 mg/kg/d for 7 days. A dosage of 2 x 2.5 mg/kg/d diminished the effectiveness of dibekacin distinctly, that of sisomicin only slightly.
对一种半合成氨基糖苷类药物3',4'-二脱氧卡那霉素(地贝卡星)在大鼠体内的肾毒性、药代动力学及治疗效果进行了评估。与其他氨基糖苷类药物一样,地贝卡星治疗导致尿中细胞及苹果酸脱氢酶排泄增加。导致尿中细胞排泄增加的最低剂量为2.5毫克/千克/天。肌肉注射5毫克/千克后地贝卡星的血清水平与其他氨基糖苷类药物相似。肾脏蓄积了大量地贝卡星,并以约7天的半衰期将其清除。重复给药后可检测到明显的蓄积倾向(肾脏最高浓度:330微克/克)。对慢性雌激素诱导的肾盂肾炎进行的实验性化疗显示,以2×5毫克/千克/天的剂量给药7天,地贝卡星和西索米星可使肾脏细菌计数显著减少。2×2.5毫克/千克/天的剂量明显降低了地贝卡星的疗效,而对西索米星的疗效影响较小。