Ngeleka M, Auclair P, Tardif D, Beauchamp D, Bergeron M G
Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Quebec, Canada.
Antimicrob Agents Chemother. 1989 Sep;33(9):1575-9. doi: 10.1128/AAC.33.9.1575.
We previously observed that the intrarenal distribution of aminoglycosides was modified by Escherichia coli endotoxin in the absence of any major renal physiological disturbance or histological changes. In the present study, we evaluated the role of E. coli endotoxin on the intrarenal distribution of vancomycin. At the beginning of the experiment, female Sprague-Dawley rats were infused intravenously with saline (control) or endotoxin (0.25 mg/kg) during 15 min. Thereafter, saline was constantly infused for the following 4 h. Two hours after the beginning of the infusion, animals were injected intravenously with a single dose of vancomycin (20 mg/kg). The drug levels in serum; renal cortex, medulla, and papilla; and urine were evaluated from 0.08 to 24 h after injection. Analysis of the area under the curve of the drug concentration in the different kidney components versus time showed a higher accumulation of vancomycin in the renal cortex and medulla in the endotoxin-infused rats than in the normal rats (P less than 0.01). Endotoxin was associated with an increase in the half-life in serum (P less than 0.01) and a lower elimination rate constant. The total clearance of vancomycin from plasma was significantly decreased in endotoxin-treated rats (P less than 0.01). These results demonstrate that endotoxin modifies the renal handling of vancomycin.
我们先前观察到，在没有任何重大肾脏生理紊乱或组织学变化的情况下，大肠杆菌内毒素会改变氨基糖苷类药物在肾内的分布。在本研究中，我们评估了大肠杆菌内毒素对万古霉素肾内分布的作用。实验开始时，在15分钟内给雌性斯普拉格-道利大鼠静脉注射生理盐水（对照组）或内毒素（0.25mg/kg）。此后，在接下来的4小时内持续输注生理盐水。输注开始两小时后，给动物静脉注射单剂量万古霉素（20mg/kg）。在注射后0.08至24小时评估血清、肾皮质、髓质和乳头以及尿液中的药物水平。对不同肾脏成分中药物浓度随时间变化的曲线下面积分析表明，输注内毒素的大鼠肾皮质和髓质中万古霉素的蓄积量高于正常大鼠（P<0.01）。内毒素与血清半衰期延长（P<0.01）和消除速率常数降低有关。内毒素处理的大鼠血浆中万古霉素的总清除率显著降低（P<0.01）。这些结果表明，内毒素会改变肾脏对万古霉素的处理。
