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 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.