Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia.
Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia.
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DOI：
10.1186/cc8206
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Chastre J
中科院分区：
文献类型：
--
作者：
Luyt CE;Clavel M;Guntupalli K;Johannigman J;Kennedy JI;Wood C;Corkery K;Gribben D;Chastre J
氨基糖苷类药物雾化吸入可能比静脉给药更好地扩散到肺泡室。这项多中心研究的目的是使用一种新的振动网孔雾化器（肺部药物递送系统（PDDS），Nektar Therapeutics）评价气雾剂递送的阿米卡星渗透到肺泡上皮细胞衬里液（ELF）中，该雾化器可向肺部递送高剂量。对28例革兰阴性VAP机械通气患者，在静脉治疗的基础上，给予阿米卡星400 mg雾化吸入，每日2次，持续7-14天。在治疗第3天，完成气雾剂递送后30分钟，所有患者在感染累及区域进行支气管肺泡灌洗，并测定ELF阿米卡星浓度。同一天，在不同时间点测定尿液和血清中阿米卡星浓度。中位（范围）ELF阿米卡星和最大血清阿米卡星浓度分别为976.1（135.7-16127.6）和0.9（0.62-1.73）μg/mL。第3天第1次和第2次12小时采集期间经尿液排泄的阿米卡星中位总量分别为19（12.21-28）和21.2（14.1-29.98）μg。在研究期间，每日至阿米卡星测量值均低于肾毒性水平。报告了64起非预期不良事件，其中2起被认为可能与雾化阿米卡星有关：1起肾衰竭恶化和1起支气管痉挛。雾化阿米卡星的PDDS递送在来自放射照相控制的感染涉及区域的ELF中实现了非常高的氨基糖苷类药物浓度，同时保持了安全的血清阿米卡星浓度。ELF浓度总是超过阿米卡星最低抑菌浓度的革兰氏阴性微生物通常负责这些肺炎。阿米卡星输送与该系统的临床影响仍有待确定。ClinicalTrials.gov标识符：NCT 01021436。
Aminoglycosides aerosolization might achieve better diffusion into the alveolar compartment than intravenous use. The objective of this multicenter study was to evaluate aerosol-delivered amikacin penetration into the alveolar epithelial lining fluid (ELF) using a new vibrating mesh nebulizer (Pulmonary Drug Delivery System (PDDS), Nektar Therapeutics), which delivers high doses to the lungs. Nebulized amikacin (400 mg bid) was delivered to the lungs of 28 mechanically ventilated patients with Gram-negative VAP for 7-14 days, adjunctive to intravenous therapy. On treatment day 3, 30 minutes after completing aerosol delivery, all the patients underwent bronchoalveolar lavage in the infection-involved area and the ELF amikacin concentration was determined. The same day, urine and serum amikacin concentrations were determined at different time points. Median (range) ELF amikacin and maximum serum amikacin concentrations were 976.1 (135.7-16127.6) and 0.9 (0.62-1.73) μg/mL, respectively. The median total amount of amikacin excreted in urine during the first and second 12-hour collection on day 3 were 19 (12.21-28) and 21.2 (14.1-29.98) μg, respectively. During the study period, daily through amikacin measurements were below the level of nephrotoxicity. Sixty-four unexpected adverse events were reported, among which 2 were deemed possibly due to nebulized amikacin: one episode of worsening renal failure, and one episode of bronchospasm. PDDS delivery of aerosolized amikacin achieved very high aminoglycoside concentrations in ELF from radiography-controlled infection-involved zones, while maintaining safe serum amikacin concentrations. The ELF concentrations always exceeded the amikacin minimum inhibitory concentrations for Gram-negative microorganisms usually responsible for these pneumonias. The clinical impact of amikacin delivery with this system remains to be determined. ClinicalTrials.gov Identifier: NCT01021436.
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DOI：
10.1164/ajrccm.152.1.7599829
发表时间：
1995-07-01
影响因子：
24.7
作者：
CHASTRE, J;FAGON, JY;GIBERT, C
通讯作者：
GIBERT, C
影响因子：
38.9
作者：
Boselli, Emmanuel;Breilh, Dominique;Allaouchiche, Bernard
通讯作者：
Allaouchiche, Bernard
DOI：
10.1016/j.ijantimicag.2003.12.019
发表时间：
2004-08-01
影响因子：
10.8
作者：
Streit, JM;Jones, RN;Fritsche, TR
通讯作者：
Fritsche, TR
DOI：
10.1164/ajrccm.165.2.2107025
发表时间：
2002-01-15
影响因子：
24.7
作者：
Goldstein, I;Wallet, F;Rouby, JJ
通讯作者：
Rouby, JJ
DOI：
10.1164/ajrccm/147.5.1279
发表时间：
1993-05-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
LECONTE, P;POTEL, G;BARON, D
通讯作者：
BARON, D