A Gamma Scintigraphy Study to Investigate Lung Deposition and Clearance of Inhaled Amikacin-Loaded Liposomes in Healthy Male Volunteers
A Gamma Scintigraphy Study to Investigate Lung Deposition and Clearance of Inhaled Amikacin-Loaded Liposomes in Healthy Male Volunteers
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DOI：
10.1089/jamp.2008.0693
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发表时间：
2009-06-01
影响因子：
3.4
通讯作者：
Perkins, Walter R.
中科院分区：
文献类型：
--
作者：
Weers, Jeffry;Metzheiser, Beth;Perkins, Walter R.
背景资料：本研究的目的是调查吸入阿米卡星的脂质体制剂在健康男性志愿者的肺沉积，清除率，和安全性雾化后与商业喷射nebulizer.Methods：阿米卡星被封装在脂质体组成的二棕榈酰磷脂酰胆碱（DPPC）和胆固醇通过一个专有的制造工艺（20毫克/毫升最终阿米卡星浓度）。脂质体用氯化锡标记法用Tc-99 m放射性标记。将120 mg标称剂量的制剂装入PARI LC星星雾化器中，使用PARI Boy压缩机雾化，受试者吸入20 min。在以下时间点，通过γ射线照相术测定3名健康男性志愿者的肺沉积结果：肺总沉积（以放射剂量的百分比表示）为32.3 +/-3.4%。放射性标记脂质体的时间依赖性保留呈双相性，最初计数快速减少，随后缓慢减少至48 h。24和48 h的总体平均滞留量分别为初始沉积剂量的60.4%和38.3%。观察到的放射性标记清除率与阿米卡星气雾剂递送至大鼠后的清除率一致。实验室参数、生命体征或ECG无临床显著变化。没有不良事件，包括咳嗽或支气管痉挛reported.Conclusions：吸入一个单一的标称剂量的120毫克脂质体阿米卡星的结果在长期保留的载药脂质体在健康志愿者的肺部。治疗耐受性良好。
Background: The purpose of this study was to investigate the inhalation of a liposomal formulation of amikacin in healthy male volunteers in terms of pulmonary deposition, clearance, and safety following nebulization with a commercial jet nebulizer.Methods: Amikacin was encapsulated in liposomes comprised of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol via a proprietary manufacturing process (20 mg/mL final amikacin concentration). The liposomes were radiolabeled with Tc-99m using the tin chloride labeling method. A nominal dose of 120 mg of drug product was loaded into a PARI LC STAR nebulizer, aerosolized using a PARI Boy compressor where subjects inhaled for 20 min. Lung deposition was determined by gamma scintigraphy in three healthy male volunteers at the following time points (0, 1, 3, 6, 12, 24, 48, and 72 h post-administration).Results: Total lung deposition, expressed as a percentage of the emitted dose, was 32.3 +/- 3.4%. The time-dependent retention of radiolabeled liposomes was biphasic with an initial rapid reduction in counts, followed by a slower phase to 48 h. The overall mean retention at 24 and 48 h was 60.4 and 38.3% of the initial dose deposited, respectively. The observed clearance of radiolabel is consistent with clearance of amikacin following aerosol delivery to rats. There were no clinically significant changes in laboratory parameters, vital signs, or ECG. No adverse events including cough or bronchospasm were reported.Conclusions: Inhalation of a single nominal dose of 120 mg liposomal amikacin results in prolonged retention of drug-loaded liposomes in the lungs of healthy volunteers. The treatment was well tolerated.