Thomas N, Toutain H, Dadoun C, Morin J P, Fillastre J P
Presse Med. 1986 Dec 20;15(46):2362-7.
A synergistic effect of antibacterial activity has been demonstrated with piperacillin combined with an aminoglycoside. Four groups of 30 female Wistar rats were injected daily for 14 days with either gentamicin 50 mg/kg, or piperacillin 1,000 mg/kg, or both drugs combined; the control group received sodium chloride in solution. In all groups, creatinine clearance, lysosomal structural latency and renal cortex enzyme activities (alanine-aminopeptidase, N-acetyl beta D-glucosaminidase, sphingomyelinase, cathepsin B) were measured on days 2, 4, 7, 10 and 14 of treatment. Renal cortex concentrations of gentamicin were measured in the group that received gentamicin alone and in the group treated with both piperacillin and gentamicin. The renal functional changes usually induced by aminoglycosides were observed. Piperacillin administered alone reduced creatinine clearance and alanine-aminopeptidase activity. The piperacillin-gentamicin combination proved unable to prevent the fall in creatinine clearance; it also reduced the alanine-aminopeptidase, sphingomyelinase and cathepsin B activities, but the reduction was less pronounced than that induced by gentamicin alone.
哌拉西林与氨基糖苷类药物联合使用已证明具有抗菌活性的协同作用。将四组每组30只雌性Wistar大鼠每天注射，持续14天，分别注射庆大霉素50mg/kg、哌拉西林1000mg/kg或两种药物联合使用；对照组接受氯化钠溶液。在治疗的第2、4、7、10和14天，测量所有组的肌酐清除率、溶酶体结构潜伏期和肾皮质酶活性（丙氨酸氨基肽酶、N-乙酰-β-D-葡萄糖苷酶、鞘磷脂酶、组织蛋白酶B）。在单独接受庆大霉素的组以及接受哌拉西林和庆大霉素联合治疗的组中测量庆大霉素的肾皮质浓度。观察到了通常由氨基糖苷类药物引起的肾功能变化。单独使用哌拉西林会降低肌酐清除率和丙氨酸氨基肽酶活性。哌拉西林-庆大霉素联合用药无法阻止肌酐清除率的下降；它还降低了丙氨酸氨基肽酶、鞘磷脂酶和组织蛋白酶B的活性，但降低程度不如单独使用庆大霉素明显。
