Coates A L, Dinh L, MacNeish C F, Rollin T, Gagnon S, Ho S L, Lands L C
Division of Respiratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
J Aerosol Med. 2000 Fall;13(3):169-78. doi: 10.1089/jam.2000.13.169.
The ability to predict drug deposition of inhaled drugs used in cystic fibrosis (CF) is important if there is a need to target specific doses of drug to the lungs of individual patients. The gold standard of measuring pulmonary deposition is the quantification of an aerosolized radiolabel either mixed with the drug solution or tagged directly to the compound of interest. Accuracy of the quantification could be assured if there is agreement between the amount of radioactivity before and after administration. Before administration, the radiolabel is concentrated in the well of the nebulizer, whereas after administration, it is distributed throughout the nebulizer, the expiratory filter and connectors, and the upper airway, stomach, trachea, and lung. Not only is the geometry of the distribution that is presented to the gamma camera different, but there are different attenuation factors for the various body tissues. The primary aim of this study was to evaluate the accuracy of the quantification of deposition. Secondary goals were to compare in vitro nebulizer performance with that measured in vivo during the deposition study. Eighty milligrams of tobramycin and technetium bound to human serum albumin was administered to 10 normal adults using a Pari LC Jet Plus (Pari Respiratory Equipment, Inc., Richmond, VA) breath-enhanced nebulizer. Techniques were developed that allowed for the accounting of 99 +/- 2% of the initial radioactivity. The fraction of the rate of lung deposition to total body deposition was the in vivo respirable fraction (0.62 +/- 0.07), which closely agreed with in vitro measurements of respirable fraction (0.62 +/- 0.04). Drug output measured from the change in weight and concentration in the nebulizer systematically overestimated drug output measured by the deposition study. The results indicate that 11.8 of the initial 80 mg would be deposited in the lungs. This technique could be adapted to accurately quantify the amount of deposition on any inhaled therapeutic agent, but caution must be used when extrapolating performance of a nebulizer on the bench to expected deposition in patients.
如果需要针对个体患者的肺部给予特定剂量的药物，那么预测用于囊性纤维化（CF）的吸入药物的药物沉积能力就很重要。测量肺部沉积的金标准是对与药物溶液混合或直接标记到感兴趣化合物上的雾化放射性标记物进行定量。如果给药前后放射性量一致，那么定量的准确性就能得到保证。给药前，放射性标记物集中在雾化器的阱中，而给药后，它分布在整个雾化器、呼气过滤器和连接器以及上呼吸道、胃、气管和肺部。不仅呈现给伽马相机的分布几何形状不同，而且不同身体组织的衰减因子也不同。本研究的主要目的是评估沉积定量的准确性。次要目标是将体外雾化器性能与沉积研究期间体内测量的性能进行比较。使用帕里LC Jet Plus（帕里呼吸设备公司，弗吉尼亚州里士满）呼吸增强型雾化器，将80毫克与人类血清白蛋白结合的妥布霉素和锝给予10名正常成年人。开发的技术能够计算出初始放射性的99±2%。肺部沉积速率与全身沉积速率的比值即为体内可吸入分数（0.62±0.07），这与体外可吸入分数测量值（0.62±0.04）非常一致。通过雾化器重量和浓度变化系统测量的药物输出量系统性地高估了沉积研究测量的药物输出量。结果表明，最初80毫克中的11.8毫克会沉积在肺部。该技术可用于准确量化任何吸入治疗剂的沉积量，但在将雾化器在实验台上的性能外推至患者预期沉积量时必须谨慎。
