Acute Hemodynamic Effects and Blood Pool Kinetics of Polystyrene Microspheres following Intravenous Administration

• Published in: Journal of pharmaceutical sciences 1981-06, Vol.70 (6), p.660-664
• Main Authors: Slack, John D., Kanke, Motoko, Simmons, Guy H., Deluca, Patrick P.
• Format: Article
• Language: English
• Subjects: acute hemodynamic effects and blood pool kinetics evaluated in dogs following intravenous administration; acute hemodynamic effects and blood pool kinetics following intravenous administration; Animals; Cerium Radioisotopes; distribution and clearance in dogs following intravenous administration; Dogs; drug delivery system; drug delivery system to target organs; Drug delivery system- polystyrene microspheres; Drug delivery system– polystyrene microspheres, acute hemodynamic effects and blood pool kinetics following intravenous administration, dogs; Female; Hemodynamics - drug effects; Injections, Intravenous; Kinetics; Kinetics-polystyrene microspheres; Kinetics—polystyrene microspheres, distribution and clearance in dogs following intravenous administration, drug delivery system; Liver - diagnostic imaging; Lung - diagnostic imaging; Microspheres; Microspheres, polystyrene—acute hemodynamic effects and blood pool kinetics following intravenous administration to dogs, drug delivery system to target organs; polystyrene-acute hemodynamic effects and blood pool kinetics following intravenous administration to dogs; Polystyrenes; potential-141Ce-labeled polystyrene microspheres; Radionuclide Imaging; Radionuclide imaging agents; Radionuclide imaging agents, potential—141Ce-labeled polystyrene microspheres, acute hemodynamic effects and blood pool kinetics evaluated in dogs following intravenous administration; Spleen - diagnostic imaging
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600700621

The acute hemodynamic effect of intravenous administration of polystyrene microspheres was investigated and correlated with their distribution pattern and kinetics. Microspheres of three diameters (3.4, 7.4, and 11.6 μm) were administered. The 7.4 and 11.6-μm diameter microspheres were filtered by the pulmonary capillary network following intravenous administration, the majority during the first pass. There was no significant hemodynamic effect following administration of the 7.4-and 11.6-μm diameter microspheres in doses as high as 3.0 × 109 and 6.1 × 108, respectively (total cross-sectional area of 1.3 × 1011 and 6.4 × 1010 μm2, respectively). Intravenous administration of 3.4-μm diameter microspheres produced significant dose-dependent systemic hypotension and depression of myocardial performance at dosages as low as 1.0 × 1010 (cross-sectional area of 9.1 × 1010 μm2). These differences in acute hemodynamic effect from the 7.4- and 11.6-μm diameter microspheres may be due to the differences in distribution kinetics and fate of the 3.4-μm diameter microspheres, which readily pass through the lungs to the systemic circulation, with late disposition primarily in the liver and spleen. Although elimination of the smaller spheres from the blood during the first 6-8 min was rapid, i.e., t 1/2 = 1.62 and 1.72 min from the venous and arterial blood circulation, respectively, levels of 103 spheres/g of blood were present in the circulation for >1hr. These findings must be considered in the planning of intravenous administration of microspheres as a drug delivery system to target organs.