1 Université François Rabelais , EA 6305, F-37032 Tours, France .
J Aerosol Med Pulm Drug Deliv. 2014 Aug;27(4):306-12. doi: 10.1089/jamp.2013.1060. Epub 2013 Dec 9.
Ventilator-associated pneumonia (VAP) caused by methicillin-resistant Staphylococcus aureus is a major cause of mortality in mechanically ventilated patients. Nebulization of teicoplanin is an alternative way of administration that may provide higher lung tissue concentrations than intravenous (IV) delivery. The aim of this study was to compare the administration of teicoplanin via aerosol with the IV route by measuring the lung and the serum teicoplanin concentrations in a rat model.
Eighty healthy male Sprague-Dawley rats were anesthetized and received a single dose of teicoplanin by the IV or aerosol route. After sacrifice, lung and blood samples were collected and teicoplanin concentrations were measured with fluorescence polarization. A noncompartmental approach was used. The area under the concentration curve/minimal inhibition concentration ratio (AUC/MIC), AUC, absorbed fraction, mean residence time (MRT), and mean absorption time (MAT) of teicoplanin were calculated.
Mean±SD lung tissue concentrations of teicoplanin in the aerosol group were significantly higher than those in the IV group (p<0.0001). The mean lung tissue concentration achieved at 15 min was 1.94±1.33 mg/g in the aerosol group and 0.04±0.01 mg/g in the IV group. The mean AUClung was 67.4 mg hr(-1)g(-1) after aerosol and 0.8 mg hr(-1)g(-1) after the IV route. In the aerosol group, AUCserum/MIC ratio was 605/2, and in the IV route, AUCserum/MIC ratio was 682/2. MAT was longer after aerosol than after the IV route (0.91 hr versus 0.06 hr), and MRT was longer after aerosol than after IV bolus administration (6.52 hr versus 5.61 hr).
Teicoplanin concentrations in the lung tissue of the rat model were significantly higher by the aerosol route than by the IV route. The AUClung after nebulization was 84 times higher than delivery by the IV route, and the AUClung/MIC ratio after nebulization met the recommended target to eradicate Staphylococcus aureus. Administration of teicoplanin by the aerosol route could represent one of the new therapeutic weapons of the treatment of the VAP.
耐甲氧西林金黄色葡萄球菌引起的呼吸机相关性肺炎（VAP）是机械通气患者死亡的主要原因。替考拉宁雾化给药是一种替代途径，可提供比静脉（IV）给药更高的肺组织浓度。本研究的目的是通过测量大鼠模型中的肺和血清替考拉宁浓度，比较替考拉宁通过雾化和 IV 途径的给药效果。
80 只健康雄性 Sprague-Dawley 大鼠麻醉后，通过 IV 或雾化途径单次给予替考拉宁。处死动物后，采集肺和血液样本，并使用荧光偏振法测量替考拉宁浓度。采用非房室模型分析。计算替考拉宁的 AUC/MIC、AUC、吸收分数、平均驻留时间（MRT）和平均吸收时间（MAT）。
与 IV 组相比，雾化组的替考拉宁肺组织浓度均显著升高（p<0.0001）。雾化组在 15 分钟时的平均肺组织浓度为 1.94±1.33mg/g，IV 组为 0.04±0.01mg/g。雾化组的 AUClung 为 67.4mg·hr(-1)·g(-1)，IV 组为 0.8mg·hr(-1)·g(-1)。在雾化组，AUCserum/MIC 比值为 605/2，IV 组为 682/2。雾化组的 MAT 长于 IV 组（0.91 小时比 0.06 小时），MRT 长于 IV 组（6.52 小时比 5.61 小时）。
在大鼠模型中，替考拉宁经雾化吸入的肺组织浓度明显高于 IV 途径。雾化后替考拉宁的 AUClung 比 IV 途径高 84 倍，雾化后 AUClung/MIC 比值达到了消除金黄色葡萄球菌的推荐目标。替考拉宁经雾化吸入给药可能成为治疗呼吸机相关性肺炎的新治疗武器之一。
