OPEN LABEL PILOT OF SAFETY, PHARMACOKINETICS, & EFFICACY OF MIKASOME

这是一项D类研究，旨在测试这样一种假设，即静脉注射MiKasome将降低囊性纤维化患者痰和支气管肺泡灌洗液中革兰氏阴性细菌的密度，这些患者体内有这些细菌。这项研究还旨在为MiKosome在囊性纤维化患者中的安全性和药代动力学数据提供依据。氨基糖苷类抗体，如阿米卡星，一直是囊性纤维化患者的主要治疗方法，这些患者因革兰氏阴性细菌肺部感染而患病。不幸的是，这类药物有相当大的毒性(主要是肾毒性和听力毒性)。将抗生素包裹在脂质体中可以通过限制在肾脏和耳朵等敏感组织中的暴露，同时保留抗生素对感染部位的输送，从而显著降低毒性。临床前研究表明，脂质体包裹的阿米卡星(MiKosome)制剂显著延长阿米卡星的半衰期，在预期的人类使用剂量范围内相对无毒，分布于肺组织，并对铜绿假单胞菌(一种经常导致囊性纤维化患者肺部感染的革兰氏阴性细菌)具有活性。进入这项研究的患者在GCRC接受评估，并在GCRC门诊接受药物输注。涉及支气管肺泡灌洗液研究的药代动力学研究将在研究队列中的5名患者身上进行。支气管肺泡灌洗将在GCRC研究内窥镜设施中进行。

This is a category D study designed to test the hypothesis that intravenous administration of MiKasome will reduce the density of gram-negative bacteria in the sputum and bronchoalveolar lavage fluids in patients with cystic fibrosis who are colonized with these bacteria. The study is also designed to provide safety and pharmacokinetic data for MiKosome in cystic fibrosis patients. Aminoglycoside antibodies, such as amikacin, have been the mainstay of therapy for cystic fibrosis patients who become ill because of gram-negative bacterial pulmonary infections. This family of drugs, unfortunately, has considerable toxicity (mainly renal toxicity and hearing toxicity). Encapsulation of antibiotics in liposomes can dramatically reduce toxicity by limiting exposure in sensitive tissues such as the kidney and the ear while preserving delivery of the antibiotic to the site of infection. Preclinical studies have demonstrated that the liposome-encapsulated formulation of amikacin (MiKosome) markedly prolongs the half-life of amikacin, is relatively non-toxic in the dose range anticipated for human usage, distributes into lung tissue, and is active against Pseudomonas aeruginosa (a gram-negative bacteria often causing pulmonary infections in patients with cystic fibrosis). Patients entering this study are evaluated in the GCRC and receive infusions of the drug in the GCRC outpatient clinic. Pharmacokinetic studies involving the study of bronchoalveolar lavage fluids will be done on five patients from the study cohort. The bronchoalveolar lavage will be performed in the GCRC Research Endoscopy facility.