Pharmacokinetics of echocontrast agent infusion in a dog model

Ultrasound contrast agents (UCAs) have a distinct diagnostic impact on tran scranial Doppler (TCD) and duplex sonography. In addition to the properties of the UCA and ultrasound imaging modes, the duration of contrast enhancem ent depends on the administration mode. infusion of UCAs may be appropriate for prolonging the diagnostically useful time of elevated Doppler intensit y. Five sedated dogs were investigated by TCD during infusion with SonoVue( TM), a new UCA consisting of sulfur hexafluoride microbubbles. The infusion rate was varied, and the time-intensity curves were analyzed. Infusion rat e of 70 ml/h provided a stable mean level of increased Doppler intensity up to 24 to 26 dB over baseline, whereas a rate of 35 ml/h did not result in a stable plateau (range 8-19 dB over baseline [5 minutes after starting tim e]). The maximum increases in Doppler mean intensity (18.2 dB [35 ml/h] and 25.6 dB [70 ml/h]) were significantly different (P = .025). Pharmacokineti c analysis of SonoVue(TM) during inflow (by exponential functional fitting of the time-mean intensity curves) and elimination (by linear regression an alysis) revealed no dose-related differences. This study demonstrated a dos e-dependent level of increased Doppler mean intensity within the brain circ ulation during infusion of SonoVue(TM). Unlike the bell-shaped course of Do ppler signal enhancement seen after bolus injection, infusion generates a s table plateau, which is an important prerequisite for more advanced contras t applications.