Pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin for the treatment of respiratory infections
Pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin for the treatment of respiratory infections
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DOI：
10.2133/dmpk.22.88
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发表时间：
2007-01-01
影响因子：
2.1
通讯作者：
Morimoto, Kazuhiro
中科院分区：
文献类型：
--
作者：
Chono, Sumio;Tanino, Tomoharu;Morimoto, Kazuhiro
通过与口服环丙沙星（CPFX）的比较，评价了肺内给药对抵抗肺泡巨噬细胞（AM）杀菌系统的病原微生物引起的呼吸道感染的药代动力学和药效学疗效。大鼠肺内注射CPFX溶液（200 μ g/kg）后，AM和肺上皮细胞衬里液（ELF）中CPFX浓度的时程明显高于口服给药（10 mg/kg）。肺内给药后血浆中CPFX浓度的时间过程明显低于AM和ELF。这些结果表明，与口服给药相比，肺内给药在将CPFX递送至AM和ELF方面更有效，尽管剂量较低，并且它避免了CPFX分布到血液中。此外，通过药代动力学/药效学分析评价了肺内给药后CPFX在AM和ELF中的抗菌作用。AMs中CPFX的浓度和ELF-时间曲线（AUQ/最小抑菌浓度（MIC）比值、AMs中CPFX的最大浓度和ELF（C-max）/MIC比值均明显高于有效值。本研究表明，肺内给药的CPFX是一种有效的技术，用于治疗呼吸道感染。
The pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin (CPFX) for the treatment of respiratory infections caused by pathogenic microorganisms resisting sterilization systems of alveolar macrophages (AMs) was evaluated by comparison with an oral administration. The time-courses of the concentration of CPFX in AMs and lung epithelial lining fluid (ELF) following intrapulmonary administration of CPFX solution to rats (200 mu g/kg) were markedly higher than that following oral administration (10 mg/kg). The time-course of the concentrations of CPFX in plasma following intrapulmonary administration was markedly lower than that in AMs and ELF. These results indicate that intrapulmonary administration is more effective in delivering CPFX to AMs and ELF, compared with oral administration, in spite of a low dose and it avoids distribution of CPFX to the blood. In addition, the antibacterial effects of CPFX in AMs and ELF following intrapulmonary administration were evaluated by pharmacokinetics/pharmacodynamics analysis. The concentration of CPFX in AMs and ELF-time curve (AUQ/minimum inhibitory concentration of CPFX (MIC) ratio and the maximum concentration of CPFX in AMs and ELF (C-max)/MIC ratio were markedly higher than the effective values. The present study indicates that intrapulmonary administration of CPFX is an effective technique for the treatment of respiratory infections.