de Jesús Valle María José, Uranga Nora Salamanca, López Francisco Gónzalez, Hurlé Alfonso Domínguez-Gil, Navarro Amparo Sánchez
Pharmacy Department, University of Salamanca, Licenciado Méndez Nieto, s/n 37007, Salamanca, Spain.
J Antimicrob Chemother. 2007 Nov;60(5):1074-9. doi: 10.1093/jac/dkm306. Epub 2007 Sep 6.
To characterize the distribution of linezolid in lung when it accesses this organ from the systemic circulation and when administered through the pulmonary route and to evaluate the influence of the 'respiratory mode' in the pulmonary distribution for both routes.
The study was conducted with 24 Wistar rats divided into four groups treated with linezolid under different experimental conditions. After the animals had been subjected to a tracheotomy followed by mechanical ventilation, the lungs were isolated. After a 5 min stabilization period, the antibiotic was administered through the systemic or the pulmonary route and samples of efferent fluid (EF) were collected using a previously programmed fraction collector. Samples of bronchoalveolar fluid (BALF) and of lung tissue were also taken at the end of each experiment. The concentrations of linezolid in the samples were determined using an HPLC technique with UV detection.
The administration of linezolid through the inhalatory route significantly increased the levels of the drug in lung tissue and BALF with lung tissue/EF partition coefficients of 8.33 +/- 2.51 as compared with 1.90 +/- 0.78 for systemic administration. Also, the decrease in respiratory rate together with the increase in tidal volume favoured the process of linezolid distribution in pulmonary tissues and fluids.
Administration through the pulmonary route affords and excellent method for passively vectoring linezolid to the pulmonary fluids and tissues and the respiratory mode seems to affect the disposition of the antibiotic in this tissue for both administration routes.
描述利奈唑胺从体循环进入肺脏以及经肺途径给药时在肺内的分布情况，并评估“呼吸模式”对两种途径在肺内分布的影响。
本研究使用24只Wistar大鼠，将其分为四组，在不同实验条件下用利奈唑胺进行治疗。动物进行气管切开并机械通气后，分离出肺脏。经过5分钟的稳定期后，通过体循环或肺途径给予抗生素，并使用预先编程的部分收集器收集流出液（EF）样本。在每个实验结束时，还采集支气管肺泡灌洗液（BALF）和肺组织样本。使用带有紫外检测的高效液相色谱技术测定样本中利奈唑胺的浓度。
经吸入途径给予利奈唑胺显著提高了肺组织和BALF中的药物水平，肺组织/EF分配系数为8.33±2.51，而经体循环给药时为1.90±0.78。此外，呼吸频率的降低以及潮气量的增加有利于利奈唑胺在肺组织和液体中的分布过程。
经肺途径给药为将利奈唑胺被动输送至肺液和组织提供了一种极佳的方法，并且呼吸模式似乎会影响两种给药途径下该抗生素在该组织中的处置情况。
