Chatzika Kalliopi, Manika Katerina, Kontou Paschalina, Pitsiou Georgia, Papakosta Despina, Zarogoulidis Konstantinos, Kioumis Ioannis
Respiratory Infections Unit, Pulmonary Department, Aristotle University of Thessaloniki, G. Papanikolaou Hospital, Thessaloniki, Greece.
Antimicrob Agents Chemother. 2014;58(3):1315-9. doi: 10.1128/AAC.02291-13. Epub 2013 Dec 9.
The aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24 in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23±1.31 mg/liter, and it was detected 7.50±2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPF was 2.96±1.45 mg/liter, but it was observed significantly earlier, at 3.58±1.38 h (P<0.001). Both groups revealed similar values of AUC24PF (31.83±23.52 versus 32.81±12.66 mg·h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11±0.74 versus 1.17±0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.
本研究旨在评估莫西沙星（MXF）在各类胸腔积液患者中的药代动力学及穿透情况。本研究纳入了12例脓胸/肺炎旁胸腔积液（PPE）患者和12例恶性胸腔积液患者。静脉注射400 mg MXF后进行单剂量药代动力学研究。给药后24小时内采集系列血浆（PL）和胸腔积液（PF）样本。通过高效液相色谱法测定PL和PF中的MXF浓度，并估算主要药代动力学参数。MXF在PF中的穿透情况通过PF中从零至24小时浓度-时间曲线下面积（AUC24）（AUC24PF）与PL中AUC24的比值来确定。尽管两组间在分布容积、清除率和消除半衰期方面存在较大个体差异，但未观察到两组在PL药代动力学方面有统计学显著差异。脓胸/PPE患者PF中的最高浓度（CmaxPF）为2.23±1.31 mg/升，在输注开始后7.50±2.39小时检测到。在恶性胸腔积液患者中，CmaxPF为2.96±1.45 mg/升，但出现时间明显更早，为3.58±1.38小时（P<0.001）。两组的AUC24PF值相似（31.83±23.52与32.81±12.66 mg·h/升）。两组患者中MXF进入PF的穿透情况同样良好（1.11±0.74与1.17±0.39）。尽管血浆药代动力学相似，但与恶性胸腔积液患者相比，脓胸/肺炎旁胸腔积液患者达到PF中MXF最高水平的时间明显延迟。然而，在两组中，由AUC24PF表示的MXF在PF中的穿透程度和局部药物暴露情况，并不因胸腔积液类型而异。
