TOBRAMYCIN ACCUMULATION IN THE RESPIRATORY SECRETIONS OF CF PATIENTS WITH REPE

患有 REPE 的 CF 患者呼吸道分泌物中妥布霉素的积累

• 批准号: 7379405
• 负责人: Margaret Rosenfeld
• 金额: $ 0.58万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379405
• 关键词: TOBRAMYCIN; ACCUMULATION; RESPIRATORY; SECRETIONS; CF

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The progressive obstructive pulmonary disease in most patients with cystic fibrosis (CF) is characterized by chronic endobronchial infection with Pseudomonas aeruginosa. Inhaled administration of anti-pseudomonal antibiotics is an attractive therapeutic option because of the ability to deliver high antibiotic concentrations to the site of infection in the endobronchial space while minimizing systemic absorption. The use of aerosolized aminoglycosides in patients with CF has been associated with improvement in lung function, decreased frequency of hospitalizations, and decreased endobronchial burden of Pseudomonas aeruginosa (1,2). Tobramycin solution for inhalation (TSI, TOBI , Chiron Corp., Seattle, WA) is approved by the U.S. Food and Drug Administration for the treatment of chronic Pseudomonas aeruginosa infection in patients with CF. It is generally prescribed for use in alternate monthly cycles, each cycle consisting of 300 mg of TSI twice daily for 28 days, followed by 28 days off therapy. The medication is delivered using a Pari LC Plus jet nebulizer with a Pulmo-aide compressor. This dosing regimen was employed in the pivotal Phase III studies of TOBI (2), and alternative dosing regimens have not been investigated. The objective of the proposed research is to assess whether tobramycin accumulates in the respiratory secretions of CF patients with mild to moderate lung disease with repeated dosing of TSI. This will be the first study to measure sputum tobramycin concentrations associated with repeated administration of TSI. Sputum induction will be utilized in order to non-invasively obtain more distal airway secretions than those produced by expectoration. Tobramycin concentrations will also be measured in expectorated sputum, as sputum expectoration is the standard means by which tobramycin concentrations have been measured in prior studies. The results of this study may lead to exploration of alternative dosing regimens for TSI. If there is evidence of accumulation of tobramycin with repeated dosing in these subjects, future studies may investigate dosing less frequently (e.g., daily) or for a shorter duration than 28 days. This is a prospective pilot study to measure tobramycin concentrations in induced and expectorated sputum at the beginning and end of a 28-day course of TSI, 300 mg twice daily.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。大多数囊性纤维化（CF）患者的进行性阻塞性肺疾病的特征是慢性铜绿假单胞菌感染了慢性支气管内感染。吸入抗卵子抗生素的施用是一种有吸引力的治疗选择，因为能够在支撑剂空间中向感染部位输送高抗生素浓度，同时最大程度地减少全身吸收。在CF患者中使用雾化的氨基糖苷与肺功能的改善，住院频率降低以及铜绿假单胞菌的支气管负担减少有关（1,2）。吸入毒素溶液（TSI，TOBI，Chiron Corp.，西雅图，华盛顿州西雅图）已获得美国食品药品监督管理局的批准，用于治疗CF患者的慢性假单胞菌铜绿病。它通常用于替代每月周期中的规定，每个周期由300 mg TSI每天两次组成，持续28天，然后进行28天的休假。使用带有Pulmo-Aide压缩机的Pari LC加喷射雾化器进行药物。这种给药方案用于TOBI的关键III期研究（2），尚未研究替代剂量方案。拟议的研究的目的是评估毒素是否在轻度至中度肺部疾病的CF患者的呼吸道分泌中积聚，并反复给予TSI。这将是第一项测量与重复给药TSI相关​​的痰毒素浓度的研究。将利用痰液诱导，以便非侵入性获得比预期的远端气道分泌物。毒素浓度也将在预期的痰液中进行测量，因为痰液期望是在先前的研究中测量毒素浓度的标准平均值。这项研究的结果可能导致对TSI的替代剂量方案的探索。如果有证据表明在这些受试者中重复给药的二霉素积累，未来的研究可能会调查剂量的频率（例如，每天）或持续时间较短，而不是28天。这是一项前瞻性试点研究，旨在测量在28天TSI的开始和结束时，每天两次300毫克的持续痰液中的毒素浓度。