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目的:研究诺氟沙星(norfloxacin,NFLX)在清醒大鼠的神经毒性和毒代动力学。方法:大鼠随机分为4组,分别ivNS,NFLX 50,100和200mg/kg。连续记录自由活动大鼠的脑电图(EEG)。用微生物法测定血清中NFLX浓度,检测菌为大肠杆菌441102。结果:(1)NFLX各组大鼠均出现痫样放电,并伴有局部抽搐、全身强直痉挛发作的行为学改变,呈剂量依赖性。脑电相对总功率增加(P<0.05)。(2)NFLX的药时曲线符合二室模型,CL,V_c和T1/2β与给药剂量无关,C_(max)和AUC_0→∞呈剂量依赖性。(3)脑电总功率的增加与剂量、C_(max)和AUC_0→∞呈正相关(r分别为0.88,0.92,0.94)。结论:本研究为量化诺氟沙星的中枢兴奋作用提供了可行 的方法,与AuC_0→∞相关的脑电相对总功率的变化可作为中枢毒性效应判定和预测的一项客观指标。
Objective: To study the neurotoxicity and toxicokinetics of norfloxacin (NFLX) in awake rats. Methods: The rats were randomly divided into 4 groups: iv NS, NFLX 50, 100 and 200 mg / kg, respectively. The electroencephalogram (EEG) of freely moving rats was continuously recorded. The concentration of NFLX in serum was determined by the microorganism method. The test strain was Escherichia coli 441102. Results: (1) All the rats in NFLX group showed epileptiform discharges accompanied by local convulsions and behavioral changes of systemic tonic spasm in a dose-dependent manner. EEG relative total power increased (P <0.05). (2) The pharmacokinetic curve of NFLX conformed to the two-compartment model. CL, V_c and T1 / 2β were independent of dose, and C_ (max) and AUC_0 → ∞ were dose-dependent. (3) The increase of EEG total power was positively correlated with dose, C max and AUC 0 → ∞ (r = 0.88, 0.92 and 0.94, respectively). CONCLUSION: This study provides a feasible method for quantifying the central excitation of norfloxacin. The change of total relative EEG power related to AuC_0 → ∞ may serve as an objective indicator for the determination and prediction of central toxic effects.