English J, Gilbert D N, Kohlhepp S, Kohnen P W, Mayor G, Houghton D C, Bennett W M
Antimicrob Agents Chemother. 1985 Jun;27(6):897-902. doi: 10.1128/AAC.27.6.897.
It is well known that in vitro the combination of carbenicillin, ticarcillin, or other antipseudomonal penicillins with gentamicin, tobramycin, or other aminoglycoside antibiotics results in the inactivation of the antibacterial activity of the aminoglycoside. To assess the influence of the in vivo interaction of tobramycin and ticarcillin on experimental nephrotoxicity, male Fischer 344 rats were given either tobramycin alone (120 mg/kg per day), tobramycin (120 mg/kg per day) and ticarcillin (250 mg/kg per day) concomitantly, or the combination of these drugs at the same doses that had been preincubated for 24 h and at the time of delivery contained but 63 and 25%, respectively, of the initial concentrations of tobramycin and ticarcillin as measured by conventional analytical procedures. Initial experiments were conducted to determine the concentrations of the antibiotics in serum achieved after administration of each test solution. After a single dose of the test solution, ticarcillin concentrations in serum were higher and more prolonged in rats given tobramycin plus ticarcillin than in rats given ticarcillin alone. After 7 days of exposure to the test solutions, inulin clearance in animals given tobramycin alone was 0.15 +/- 0.1 (mean +/- 2 standard errors) ml/min per 100 g of body weight as compared with 0.53 +/- 0.1 in rats given tobramycin and ticarcillin concomitantly, 0.59 +/- 0.1 in animals given the partially inactivated tobramycin-ticarcillin mixture, and 0.79 +/- 0.1 in control rats. Although there was some improvement in inulin clearance in the group containing tobramycin alone, the three treatment groups maintained the same rank relationship in inulin clearance through 14 days of treatment. Real histology confirmed the attenuation of tubular injury in animals given tobramycin and ticarcillin concomitantly. There was no evidence of toxicity from the presumed inactivation complexes of tobramycin-ticarcillin. These results document an in vivo protective effect of ticarcillin on experimental tobramycin nephrotoxicity.
众所周知，在体外，羧苄西林、替卡西林或其他抗假单胞菌青霉素与庆大霉素、妥布霉素或其他氨基糖苷类抗生素联合使用会导致氨基糖苷类抗生素的抗菌活性丧失。为了评估妥布霉素和替卡西林在体内的相互作用对实验性肾毒性的影响，给雄性Fischer 344大鼠分别单独给予妥布霉素（每天120mg/kg）、同时给予妥布霉素（每天120mg/kg）和替卡西林（每天250mg/kg），或给予以相同剂量预先孵育24小时的这两种药物的组合，在给药时，通过常规分析程序测得，妥布霉素和替卡西林的初始浓度分别仅为63%和25%。进行初始实验以确定给予每种测试溶液后血清中抗生素的浓度。给予单剂量测试溶液后，同时给予妥布霉素和替卡西林的大鼠血清中替卡西林浓度高于单独给予替卡西林的大鼠，且持续时间更长。暴露于测试溶液7天后，单独给予妥布霉素的动物的菊粉清除率为每100g体重0.15±0.1（平均值±2个标准误）ml/min，而同时给予妥布霉素和替卡西林的大鼠为0.53±0.1，给予部分失活的妥布霉素 - 替卡西林混合物的动物为0.59±0.1，对照大鼠为0.79±0.1。尽管单独给予妥布霉素的组中菊粉清除率有一定改善，但在为期14天的治疗中，三个治疗组在菊粉清除率方面保持相同的等级关系。实际组织学证实了同时给予妥布霉素和替卡西林的动物肾小管损伤减轻。没有证据表明妥布霉素 - 替卡西林的假定失活复合物具有毒性。这些结果证明了替卡西林对实验性妥布霉素肾毒性的体内保护作用。
