Disposition of perfluorobutane in rats after intravenous injection of Sonazoid.
The new ultrasound contrast agent Sonazoid was injected IV in rats at doses of 0.8 and 8 muL perfluorobutane (PFB)-containing microbubbles/kg body weight. Samples were obtained from blood, liver, spleen, fat, kidney, muscle, heart, lung and brain from both males and females and the PFB gas was analyzed using validated gas chromatography mass spectrometry methods. No differences were observed between genders or doses for any of the pharmacokinetic parameters. For all tissues, the highest concentrations were observed at the first time point (i.e., 5 min postinjection) (51% of injected dose in liver; total recovery of 69%). The highest concentrations of PFB in tissue were observed in spleen > liver > lung > kidney >> other tissues. At 24 h after dosing, the total amount of PFB remaining in the tissues was 1.9%. These data fit well with the finding that after a Sonazoid dose of 8 microL microbubbles/kg to male rats, more than 50% of the injected PFB was recovered in exhaled air by 20 min after dosing. During the first 24 h after administration, more than 96% of the PFB dose was recovered in exhaled air.
Toft
Kim Gunnar
KG
Research and Development, GE Healthcare Bio-Sciences, Oslo, Norway. kim.toft@ge.com
Hustvedt
Svein Olaf
SO
Hals
Petter-Arnt
PA
Oulie
Inger
I
Uran
Steinar
S
Landmark
Kristin
K
Normann
Per Trygve
PT
Skotland
Tore
T
D000818:Animals; D001944:Breath Tests; D003287:Contrast Media / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D005466:Fluorocarbons / Q000032:analysis / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage*; D008297:Male; D045423:Microbubbles; D010087:Oxides / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003287:Contrast Media; D005290:Ferric Compounds; D005466:Fluorocarbons; D010087:Oxides; C069727:Sonazoid; D007501:Iron; C108042:perfluorobutane