Breilh D, Jougon J, Djabarouti S, Gordien J B, Xuereb F, Velly J F, Arvis P, Landreau V, Saux M C
Pharmacokinetic and Clinical Pharmacy Department, Haut-Lévêque Hospital, Pessac, France.
J Chemother. 2003 Dec;15(6):558-62. doi: 10.1179/joc.2003.15.6.558.
The degree of penetration of an antibiotic into the infection site is an important factor for its therapeutic efficacy, particularly in respiratory tract infections. In the present study, we examined the lung tissue diffusion of moxifloxacin at a dose of 400 mg administered intravenously or orally once-daily, and the results were correlated to microbiological data to estimate the clinical efficacy of moxifloxacin in lower community-acquired respiratory infections. This was a prospective, randomized, parallel-group trial, open-label, single-center study. Patients undergoing lung surgery for bronchial cancer which necessitates the removal of an anatomical piece of lung tissue were randomized into twelve treatment groups, dependent upon the time of surgery and the moxifloxacin formulation, i.v. or oral, administered. During surgery, one blood sample was taken at the time of tissue collection to determine moxifloxacin plasma concentration. At the same time, tissue samples were taken by pulmonary exeresis. A validated new high performance liquid chromatography assay was used to determine moxifloxacin concentrations in plasma and lung tissue. A total of 49 patients (25 for i.v. administration, 24 for oral administration, 44 men and 5 women, mean age, 61 years, mean body weight, 72 kg, mean creatinine clearance was 84 ml/min/1.73 m2) were enrolled. The mean +/- SD steady-state moxifloxacin ratios between lung and plasma concentrations were respectively: 3.53 +/- 1.89 and 4.36 +/- 1.48 for i.v. and oral administration. The mean steady-state moxifloxacin maximal lung concentrations (Cmax) were respectively 12.37 microg/g and 16.21 microg/g for i.v. and oral administration. Moxifloxacin both intravenously and orally exhibits high penetration in lung tissue, with tissue concentrations far above the MIC90s for most of the susceptible pathogens commonly involved, thus underlining its suitability for the treatment of community-acquired, lower respiratory tract infections.
抗生素渗入感染部位的程度是影响其治疗效果的一个重要因素，在呼吸道感染中尤为如此。在本研究中，我们检测了每日静脉或口服一次400mg剂量莫西沙星在肺组织中的扩散情况，并将结果与微生物学数据相关联，以评估莫西沙星在社区获得性下呼吸道感染中的临床疗效。这是一项前瞻性、随机、平行组、开放标签、单中心研究。因支气管癌接受肺手术且需要切除一块解剖肺组织的患者，根据手术时间和莫西沙星剂型（静脉注射或口服）被随机分为12个治疗组。手术期间，在采集组织时采集一份血样以测定莫西沙星血浆浓度。同时，通过肺切除术采集组织样本。采用经过验证的新型高效液相色谱法测定血浆和肺组织中的莫西沙星浓度。共纳入49例患者（静脉给药25例，口服给药24例，男性44例，女性5例，平均年龄61岁，平均体重72kg，平均肌酐清除率为84ml/min/1.73m²）。静脉注射和口服给药时，肺与血浆浓度之间的平均±标准差稳态莫西沙星比值分别为：3.53±1.89和4.36±1.48。静脉注射和口服给药时，稳态莫西沙星最大肺浓度（Cmax）分别为12.37μg/g和16.21μg/g。莫西沙星静脉注射和口服在肺组织中均表现出高渗透性，组织浓度远高于大多数常见易感病原体的MIC90，因此突出了其治疗社区获得性下呼吸道感染的适用性。
