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双氯芬酸对兔眼内炎模型中环丙沙星和洛美沙星眼内浓度的影响。

Effect of diclofenac on ocular levels of ciprofloxacin and lomefloxacin in rabbits with endophthalmitis.

作者信息

Krustev Svetozar Zhelev, Rusenova Nikolina Velizarova, Haritova Aneliya Milanova

机构信息

Department of Veterinary Surgery .

出版信息

Drug Dev Ind Pharm. 2014 Nov;40(11):1459-62. doi: 10.3109/03639045.2013.828225. Epub 2013 Aug 13.

Abstract

The purpose of this study was to analyze ciprofloxacin and lomefloxacin penetration into the anterior eye tissues after topical instillation in healthy rabbits and with experimental Staphylococcus aureus endophthalmitis. Additionally, effect of diclofenac sodium eye drops on the distribution of both fluoroquinolones in the inflamed eye tissues was investigated. An intense protocol with frequent antibiotic administration was chosen. Samples from aqueous humor were obtained 2 and 6 h after the start of the treatment. Samples from cornea and iris were obtained at the end of the experiment, after euthanasia of the animals. Drug concentrations were measured by HPLC method. The median levels of ciprofloxacin and lomefloxacin in aqueous humor of healthy animals, 2 and 6 h after drug administration were 6.39-9.65 and 5.30-6.81 µg/ml, respectively. Ciprofloxacin levels were neither changed from the inflammation nor after instillation of diclofenac. In contrary, lomefloxacin concentrations in aqueous humour of inflamed eye were significantly increased 12.15-15.08 µg/ml, especially after diclofenac administration (17.12-27.76 µg/ml). Levels of both fluoroquinolones in cornea (13.08 µg/g for ciprofloxacin and 12.25 µg/g for lomefloxacin) and in iris (0.84 µg/g for ciprofloxacin and 1.34 µg/g for lomefloxacin) were higher than MIC and MBC values against S. aureus ATCC 25923. Although higher lomefloxacin concentrations were observed in the aqueous humor after instillation of diclofenac, the levels of both fluoroquinolones in iris and in cornea were not significantly changed. Topical administration of lomefloxacin and diclofenac in combination improved penetration of the antibacterial agent in the aqueous humor which can be of clinical importance.

摘要

本研究的目的是分析环丙沙星和洛美沙星在健康兔及实验性金黄色葡萄球菌性眼内炎局部滴注后在前眼部组织中的渗透情况。此外,还研究了双氯芬酸钠滴眼液对两种氟喹诺酮类药物在炎症眼组织中分布的影响。选择了频繁使用抗生素的强化方案。在治疗开始后2小时和6小时采集房水样本。在实验结束时,对动物实施安乐死后采集角膜和虹膜样本。采用高效液相色谱法测定药物浓度。给药后2小时和6小时,健康动物房水中环丙沙星和洛美沙星的中位水平分别为6.39 - 9.65μg/ml和5.30 - 6.81μg/ml。环丙沙星水平在炎症状态下以及滴注双氯芬酸钠后均未改变。相反,炎症眼房水中洛美沙星浓度显著升高至12.15 - 15.08μg/ml,尤其是在滴注双氯芬酸钠后(17.12 - 27.76μg/ml)。两种氟喹诺酮类药物在角膜(环丙沙星为13.08μg/g,洛美沙星为12.25μg/g)和虹膜(环丙沙星为0.84μg/g,洛美沙星为1.34μg/g)中的水平均高于对金黄色葡萄球菌ATCC 25923的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)值。尽管滴注双氯芬酸钠后房水中观察到较高的洛美沙星浓度,但两种氟喹诺酮类药物在虹膜和角膜中的水平均未显著改变。联合局部应用洛美沙星和双氯芬酸钠可提高抗菌剂在房水中的渗透率,这可能具有临床意义。

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