Vorbach H, Weigel G, Robibaro B, Schaumann R, Hlousek M, Beil W J, Griesmacher A, Georgopoulos A, Graninger W
Department of Infectious Diseases, University Hospital of Vienna, Austria.
Int J Clin Pharmacol Ther. 1997 Jun;35(6):235-8.
One local side-effect closely related to the use of parenteral fluoroquinolones is phlebitis. The occurrence of this phenomenon is largely thought due to the damage of endothelial cells with subsequent inflammation. In order to evaluate the effect of ciprofloxacin, fleroxacin, and ofloxacin on the viability of human umbilical venous endothelial cells (HUVEC), intracellular ATP levels were measured by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined by means of direct radioimmunoassay. Commercially available preparations of ciprofloxacin (2 mg/ml) and fleroxacin (4 mg/ml) reduced the intracellular ATP content by 75.9 +/- 1.9% and 82.1 +/- 0.6%, respectively, within 20 minutes, indicating severe damage of endothelial cells. Incubation with ofloxacin (2 mg/ml) did not have any detrimental effect. All fluoroquinolones were tolerated well by endothelial cells at low concentrations up to 20 micrograms/ml. Concentrations between 100-200 micrograms/ml gradually led to functional alterations such as increased PGI2 release. The tolerance of intravenously applied antibiotics has been tested in animal models. Use of human venous endothelial cells for testing antibiotic solutions for intravenous application provides a valuable alternate model for tolerability.
与胃肠外使用氟喹诺酮类药物密切相关的一种局部副作用是静脉炎。这种现象的发生在很大程度上被认为是由于内皮细胞受损继而引发炎症所致。为了评估环丙沙星、氟罗沙星和氧氟沙星对人脐静脉内皮细胞（HUVEC）活力的影响，采用荧光素 - 荧光素酶测定法测量细胞内ATP水平。通过直接放射免疫测定法测定前列环素（PGI2）和血栓素A2（TXA2）。市售的环丙沙星制剂（2mg/ml）和氟罗沙星制剂（4mg/ml）在20分钟内分别使细胞内ATP含量降低了75.9±1.9%和82.1±0.6%，表明内皮细胞受到严重损伤。用氧氟沙星（2mg/ml）孵育没有任何有害影响。所有氟喹诺酮类药物在浓度高达20μg/ml时内皮细胞耐受性良好。100 - 200μg/ml之间的浓度会逐渐导致功能改变，如PGI2释放增加。已在动物模型中测试了静脉应用抗生素的耐受性。使用人静脉内皮细胞来测试静脉应用的抗生素溶液为耐受性提供了一种有价值的替代模型。
