Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys
Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys
复制标题
甲磺酸粘菌素 (CMS) 和 CMS 雾化后粘菌素在狒狒体内的药代动力学
作者：
S. Marchand;S. Bouchène;M. Monte;L. Guilleminault;J. Montharu;María Cabrera;N. Grégoire;P. Gobin;P. Diot;W. Couet;L. Vecellio
这项研究的目的是比较两种不同的雾化器：eFlow Rapid®和Pari LC STAR®，通过闪烁成像和PK建模来模拟恒定支气管雾化后，从测量的血浆浓度中模拟上皮衬里液体浓度。3只狒狒静脉注射CMS，皮下注射2种气雾剂和粘菌素。雾化后进行伽马成像，以确定粘菌素在肺部的分布。在9h内采集血样，用LC-MS/MS测定粘菌素和CMS的血浆浓度，进行群体药代动力学分析和模拟预测雾化吸入后的肺浓度。用Pari LC®STAR雾化吸入CMS比雾化吸入eFlow Rapid®雾化吸入的气雾剂在肺内的分布更高。CMS在肺内沉积的比例(分别为3.5%和1.3%)证实了这一观察结果。使用Pari LC STAR®系统后，CMS和粘菌素在上皮衬里液体中的模拟浓度高于eFlow快速®系统。雾化后，一小部分CMS进入肺部，但Pari LC Star®系统比eFlow Rapid®系统测量到更高的粘菌素血浆浓度，并模拟更高的肺内粘菌素浓度。
The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.