Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties
Pharmacotherapeutic group: Ultrasound contrast media.
ATC code: VO8DA05.

Sulphur hexafluoride is an inert, innocuous gas, poorly soluble in aqueous solutions. There are literature reports of the use of the gas in the study of respiratory physiology and in pneumatic retinopexy. The addition of sodium chloride 9 mg/mL (0.9%) solution for injection to the lyophilised powder followed by vigorous shaking results in the production of the microbubbles of sulphur hexafluoride. The microbubbles have a mean diameter of about 2.5 µm, with 90% having a diameter less than 6 µm and 99% having a diameter less than 11 µm. Each millilitre of SonoVue contains 8 µL of the microbubbles. The intensity of the reflected signal is dependent on concentration of the microbubbles and frequency of the ultrasound beam. The interface between the sulphur hexafluoride bubble and the aqueous medium acts as a reflector of the ultrasound beam thus enhancing blood echogenicity and increasing contrast between the blood and the surrounding tissues.

Intravenous use
At the proposed clinical doses for intravenous administration, SonoVue has been shown to provide marked increase in signal intensity of more than 2 minutes for B-mode imaging in echocardiography and of 3 to 8 minutes for Doppler imaging of the macrovasculature and microvasculature.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

The total amount of sulphur hexafluoride administered in a clinical dose is extremely small, (in a 2 mL dose the microbubbles contain 16 µL of gas). The sulphur hexafluoride dissolves in the blood and is subsequently exhaled.

After a single intravenous injection of 0.03 or 0.3 mL of SonoVue/kg (approximately 1 and 10 times the maximum clinical dose) to human volunteers, the sulphur hexafluoride was cleared rapidly. The mean terminal half-life was 12 minutes (range 2 to 33 minutes). More than 80% of the administered sulphur hexafluoride was recovered in exhaled air within 2 minutes after injection and almost 100% after 15 minutes.

In patients with diffuse interstitial pulmonary fibrosis, the percent of dose recovered in expired air averaged 100% and the terminal half-life was similar to that measured in healthy volunteers.