Fischman A J, Livni E, Babich J W, Alpert N M, Bonab A, Chodosh S, McGovern F, Kamitsuka P, Liu Y Y, Cleeland R, Prosser B L, Correia J A, Rubin R H
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA.
Antimicrob Agents Chemother. 1996 Mar;40(3):659-64. doi: 10.1128/AAC.40.3.659.
The pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, were measured by positron emission tomography (PET) with [18F]fleroxacin in five patients with acute bacterial exacerbations of chronic bronchitis and in five patients with symptomatic, complicated urinary tract infection. Two studies were performed with each patient, one within 24 h of the initiation and one within 24 h of the completion of a 7-day course of fleroxacin, 400 mg/day. For each study, the patient received an infusion of that day's therapeutic dose of fleroxacin (400 mg) supplemented with approximately 740 MBq of [18F]fleroxacin, and serial PET images and blood samples were collected for 6 to 8 h starting at the initiation of the infusion. Between studies, the drug was administered orally. In all infected tissues, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. In kidneys, accumulation was greater in the presence of active infection (P < 0.01), while in lungs, accumulation was lower (P < 0.02). Infection of the lung or urinary tract had no effect on drug delivery to uninvolved tissues. Also, there was no difference between the results obtained at the beginning and the end of therapy. Overall, peak concentrations of drug many times the MIC at which 90% of the infecting organisms are inhibited (MIC90) were achieved in the kidneys (> 30 micrograms/g), prostate glands (> 11 micrograms/g), and lungs (> 14 micrograms/g). Plateau concentrations (2 to 8 h; given as mean micrograms per gram +/- standard error of the mean) of drug in kidneys (15.11 +/- 0.55), prostate glands (5.08 +/- 0.19), and lungs (5.75 +/- 0.22) were also well above the MIC90 for most relevant pathogens. All patients had a good therapeutic response to fleroxacin.
采用正电子发射断层扫描（PET）技术，以[18F]氟罗沙星对5例慢性支气管炎急性细菌感染加重患者和5例有症状的复杂性尿路感染患者进行检测，以测定新型广谱氟喹诺酮类药物氟罗沙星的药代动力学。对每位患者进行两项研究，一项在开始服用氟罗沙星（400mg/天）7天疗程的24小时内进行，另一项在该疗程结束的24小时内进行。每项研究中，患者接受当日治疗剂量的氟罗沙星（400mg）静脉输注，并补充约740MBq的[18F]氟罗沙星，从输注开始起6至8小时内收集系列PET图像和血样。两项研究之间，药物改为口服给药。在所有感染组织中，放射性标记药物迅速蓄积，输注结束后1小时内达到稳定水平。在肾脏中，有活动性感染时蓄积量更大（P<0.01），而在肺部，蓄积量较低（P<0.02）。肺部或尿路感染对药物向未受累组织的输送无影响。此外，治疗开始时和结束时获得的结果无差异。总体而言，在肾脏（>30微克/克）、前列腺（>11微克/克）和肺部（>14微克/克）达到的药物峰值浓度是抑制90%感染菌的最低抑菌浓度（MIC90）的许多倍。肾脏（15.11±0.55）、前列腺（5.08±0.19）和肺部（5.75±0.22）药物的平台期浓度（2至8小时；以每克微克平均数±平均数标准误表示）也远高于大多数相关病原体的MIC90。所有患者对氟罗沙星均有良好的治疗反应。
