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

这是一项D类研究，旨在检验MiKasome静脉给药将降低囊性纤维化患者痰液和支气管肺泡灌洗液中革兰氏阴性菌密度的假设，这些患者的痰液和支气管肺泡灌洗液中存在革兰氏阴性菌。 该研究还旨在提供MiKosome在囊性纤维化患者中的安全性和药代动力学数据。 氨基糖苷类抗体，如阿米卡星，一直是治疗囊性纤维化患者的主要药物，这些患者因革兰氏阴性细菌肺部感染而患病。 不幸的是，这类药物具有相当大的毒性（主要是肾毒性和听力毒性）。 将抗生素包封在脂质体中可以通过限制在敏感组织如肾脏和耳朵中的暴露而显著降低毒性，同时保持抗生素向感染部位的递送。 临床前研究已经证明，阿米卡星的脂质体包封制剂（MiKosome）显著延长阿米卡星的半衰期，在预期用于人类使用的剂量范围内相对无毒，分布到肺组织中，并且对铜绿假单胞菌（一种革兰氏阴性细菌，通常在囊性纤维化患者中引起肺部感染）有活性。 进入本研究的患者在GCRC中进行评价，并在GCRC门诊接受药物输注。 将对研究队列中的5例患者进行涉及支气管肺泡灌洗液研究的药代动力学研究。 支气管肺泡灌洗将在GCRC Research Endoscopy机构进行。

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.