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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients
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Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients

机译：危重患者气雾剂递送和CMS静脉内给药后粘菌素甲磺酸酯（CMS）和粘菌素的肺内和全身药代动力学比较

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Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n - 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients.
机译：Colistin是一种旧的抗生素，最近在治疗由​​于多重耐药的革兰氏阴性菌引起的肺部感染方面已引起了广泛的关注。雾化似乎是一种有前途的给药方式，但粘菌素是一种无活性的前药，粘菌素甲磺酸盐（CMS）。然而，在重症患者中，活性部分的肺内浓度之间的差异作为给药途径的函数尚未得到精确记录。在这项研究中，在两次通过气雾剂递送接受了200万国际单位（MIU）CMS的重症患者（n-12）的血浆和上皮内衬液（ELF）中，分别测量了CMS和粘菌素的浓度静脉内给药。使用群体方法进行药代动力学分析，并通过药代动力学-药效学（PK-PD）建模和模拟完成。 ELF粘菌素的浓度相差很大（9.53至1,137 mg / l），但比气雾剂给药后血浆中的浓度（0.15至0.73 mg / l）要高得多，但在静脉内施用CMS后却没有。 CMS气雾剂递送后，通常有9％的CMS剂量达到了ELF，只有1.4％的系统性转化为粘菌素。 PK-PD分析得出的结论是，CMS气雾剂递送后的抗菌功效要比静脉内施用后高得多。这些新数据似乎支持使用CMS气雾剂递送治疗重症监护患者的肺部感染。

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