Physiologically based pharmacokinetic model for fluorocarbon elimination after the administration of an octafluoropropane-albumin microsphere sonographic contrast agent

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 i n proteinaceous microspheres, injected intravenously for use as a myocardia l contrast agent in humans. This model has sis compartments: two lung compa rtments (alveolar and dead volume), and compartments for the heart, slowly perfused tissue, richly perfused tissue, and gastrointestinal tract. The mo del was developed to determine the distribution and excretion of the octafl uoropropane in the body. Despite the high affinity of octafluoropropane for tissue, the model predicted that nearly 100% of the material would be exha led 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 pl ay a critical role in the complete excretion of this contrast agent. The ph ysiologically 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.