AI-700 pharmacokinetics, tissue distribution and exhaled elimination kinetics in rats.
The purpose of these studies was to determine the pharmacokinetics, tissue distribution, and exhaled elimination kinetics in rats for intravenously administered AI-700, which consists of porous microspheres containing decafluorobutane (DFB), for use as an ultrasound contrast agent. [Pd]-AI-700 was administered intravenously to rats (10 mg microspheres/kg). Blood and tissue samples collected at specified times were analyzed for palladium by inductively coupled plasma-mass spectrometry (ICP-MS). AI-700 was also administered intravenously to rats (40 mg microspheres/kg) and expired air was collected over time. Expired air samples were analyzed for DFB by validated adsorbent trapping-thermal desorption-gas chromatography-mass spectrometry methodology. Pd from [Pd]-AI-700 was cleared from blood with a ca. 50-85% decline from peak concentration within 5 min. At 1440 min post-dose, 52-72% of the Pd dose was recovered from organs of the reticuloendothelial system. Approximately 77% of the intravenously injected DFB was found in expired air within 3h after dosing, with most of the DFB dose (61+/-6%) expired within the first 10 min after dosing. As expected, the microspheres were cleared through the reticuloendothelial system, and the DFB was eliminated in expired air, with more than half of the DFB eliminated within the first 10 min after dosing.
Straub
Julie A
JA
Acusphere, Inc., Watertown, MA 02472, USA. julie.straub@acusphere.com
Chickering
Donald E
DE
Hartman
Thomas G
TG
Gloff
Carol A
CA
Bernstein
Howard
H
D000388:Air / Q000032:analysis; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D008168:Lung / Q000378:metabolism; D008297:Male; D008863:Microspheres; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D010165:Palladium; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003287:Contrast Media; D005466:Fluorocarbons; D010165:Palladium; C108042:perfluorobutane