Hutter J C, Luu H M, Mehlhaff P M, Killam A L, Dittrich H C
Center for Devices and Radiological Health, United States Food and Drug Administration, Rockville, MD 20852, USA.
J Ultrasound Med. 1999 Jan;18(1):1-11. doi: 10.7863/jum.1999.18.1.1.
A physiologically based pharmacokinetic model was developed to evaluate the kinetics of one of the newest sonographic contrast agents available, FS069 or Optison. This material consists of octafluoropropane gas encapsulated in proteinaceous microspheres, injected intravenously for use as a myocardial contrast agent in humans. This model has six compartments: two lung compartments (alveolar and dead volume), and compartments for the heart, slowly perfused tissue, richly perfused tissue, and gastrointestinal tract. The model was developed to determine the distribution and excretion of the octafluoropropane in the body. Despite the high affinity of octafluoropropane for tissue, the model predicted that nearly 100% of the material would be exhaled from the lungs within 6 min. The model verified the results of a phase I clinical trial with 10 healthy subjects. Ventilation rate was found to play a critical role in the complete excretion of this contrast agent. The physiologically based pharmacokinetic model was a useful tool for evaluating the safety of FS069. This model can be used a basis for developing similar models for other types of contrast agents.
建立了一个基于生理的药代动力学模型，以评估最新的超声造影剂之一FS069或Optison的动力学。这种物质由包裹在蛋白质微球中的八氟丙烷气体组成，通过静脉注射用作人体心肌造影剂。该模型有六个隔室：两个肺部隔室（肺泡和无效腔），以及心脏、灌注缓慢组织、灌注丰富组织和胃肠道的隔室。开发该模型是为了确定八氟丙烷在体内的分布和排泄情况。尽管八氟丙烷对组织具有高亲和力，但该模型预测，近100%的物质将在6分钟内从肺部呼出。该模型验证了一项针对10名健康受试者的I期临床试验结果。发现通气率在这种造影剂的完全排泄中起关键作用。基于生理的药代动力学模型是评估FS069安全性的有用工具。该模型可作为为其他类型造影剂开发类似模型的基础。
