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

Abstract

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.

Enhancement of ultrasonic thrombus imaging using novel liposomal bubbles targeting activated platelet glycoprotein IIb/IIIa complex—in vitro and in vivo study

“…The RGD peptide is an octapeptide and is considered to be nontoxic and non-immunogenic [26,27]. Perfluoropropane is an inert gas, used as a constituent of commercially available echo contrast agents such as Optison and Definity [33], and is exhaled from the lungs [34]. Therefore, this echo contrast agent is generally considered nontoxic, although safety in humans remains to be demonstrated.…”

Definition of Contrast Enhancement Phases of the Liver Using a Perfluoro-Based Microbubble Agent, Perflubutane Microbubbles

“…Because of the high temporal and spatial resolution of ultrasonography, contrast-enhanced ultrasonography with perfluoro-based MB agents can visualize the vasculature and perfusion of the lesions continuously, which has resulted in high accuracy in characterizing lesions (Jang et al 2007;Wilson et al 2008). However, it is known that disposition of the MB agents, even among the perfluoro-based agents, differs with the composition of the gas and shell materials (Hutter et al 1999;Toft et al 2006). Therefore, investigating the dynamics of respective MB agents in the liver is of great significance for the standardization of liver contrast ultrasonography.…”

A respiration–metabolism chamber system and a GC–MS method developed for studying exhalation of perfluorobutane in rats after intravenous injection of the ultrasound contrast agent Sonazoid™

“…There is, however, one report describing blood and exhalation kinetics of perfluoropropane after injection of Optison TM in mongrel dogs [7] and one report describing exhalation kinetics of the same agent in humans [8]. Moreover, there is one report describing blood and exhalation kinetics of perfluoropentane after injection of EchoGen TM in humans [9].…”