Ohnishi A, Bryant T D, Branch K R, Sabra R, Branch R A
Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee 37232.
Antimicrob Agents Chemother. 1989 Jun;33(6):928-32. doi: 10.1128/AAC.33.6.928.
Coadministration of sodium ticarcillin with an aminoglycoside is known to reduce the nephrotoxicity of the aminoglycoside. However, it is not known whether the penicillin or the obligatory sodium load confers protection. To investigate this, gentamicin has been administered intraperitoneally in doses of 50, 60, or 80 mg/kg per day for 12 days in groups of rats receiving either a normal or a low sodium intake. Alterations in creatinine clearance have been measured. Salt depletion resulted in an enhanced nephrotoxic response with a shift in the dose-response curve to the left. Administration of sodium ticarcillin to rats with a salt-depleted intake at a dose sufficient to replace sodium intake conferred an equal degree of protection to rats with a normal salt intake. We report that the obligatory salt supplement with ticarcillin is sufficient to account for the renal sparing effect of the combination treatment without having to infer a direct chemical interaction of penicillin with the aminoglycoside.
已知替卡西林钠与氨基糖苷类药物联合使用可降低氨基糖苷类药物的肾毒性。然而，尚不清楚是青霉素还是必需的钠负荷起到了保护作用。为了对此进行研究，已对正常钠摄入量或低钠摄入量的大鼠组腹腔注射庆大霉素，剂量为每天50、60或80mg/kg，持续12天。测量了肌酐清除率的变化。盐耗竭导致肾毒性反应增强，剂量反应曲线向左移动。以足以补充钠摄入量的剂量给钠耗竭的大鼠注射替卡西林钠，给予了与正常盐摄入量大鼠同等程度的保护。我们报告，替卡西林必需的盐补充剂足以解释联合治疗的肾脏保护作用，而无需推断青霉素与氨基糖苷类药物之间存在直接的化学相互作用。
