Wold J S, Turnipseed S A, Broddle W D, Owen N V
Antimicrob Agents Chemother. 1977 Oct;12(4):465-9. doi: 10.1128/AAC.12.4.465.
Because of the potential for an interaction between cephalosporins and aminoglycosides leading to renal injury, an evaluation of the effect of a new cephalosporin, cefamandole nafate, on the toxicity of the aminoglycoside tobramycin was performed in laboratory animals. High doses of cefamandole nafate did not increase the acute toxicity (lethality) of tobramycin in rats or mice. In a subacute experiment in rats, dose-related tobramycin nephrotoxicity, as evidenced by blood urea nitrogen changes, increased kidney weights, and histologically determined tubular nephrosis and necrosis, was observed. Concomitant treatment with cefamandole nafate, 500 mg/kg, did not increase tobramycin nephrotoxicity, but protected against the aminoglycoside-induced renal injury. Determination of tissue radioactivity after administration of [(14)C]tobramycin indicated that cefamandole nafate treatment resulted in uniformly lower tobramycin tissue concentrations compared with the control, suggesting that the protective effect was produced by enhanced excretion of tobramycin after cefamandole nafate treatment.
由于头孢菌素与氨基糖苷类药物之间可能存在相互作用，从而导致肾损伤，因此在实验动物中评估了一种新型头孢菌素头孢孟多酯钠对氨基糖苷类药物妥布霉素毒性的影响。高剂量的头孢孟多酯钠并未增加妥布霉素对大鼠或小鼠的急性毒性（致死率）。在大鼠的一项亚急性实验中，观察到与剂量相关的妥布霉素肾毒性，表现为血尿素氮变化、肾脏重量增加以及组织学确定的肾小管肾病和坏死。同时给予500mg/kg的头孢孟多酯钠并未增加妥布霉素的肾毒性，反而对氨基糖苷类药物引起的肾损伤具有保护作用。给予[¹⁴C]妥布霉素后测定组织放射性表明，与对照组相比，头孢孟多酯钠治疗导致妥布霉素组织浓度普遍降低，这表明头孢孟多酯钠治疗后增强的妥布霉素排泄产生了保护作用。
