RT Journal Article
SR Electronic
T1 Preclinical and Clinical Evidence for Disappearance of Long-Circulating Characteristics of Polyethylene Glycol Liposomes at Low Lipid Dose
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 996
OP 1001
VO 293
IS 3
A1 Peter Laverman
A1 Adrienne H. Brouwers
A1 Els Th. M. Dams
A1 Wim J. G. Oyen
A1 Gert Storm
A1 Nico van Rooijen
A1 Frans H. M. Corstens
A1 Otto C. Boerman
YR 2000
UL http://jpet.aspetjournals.org/content/293/3/996.abstract
AB This study describes the effect of the lipid dose of99mTc-polyethylene glycol (PEG) liposomes in the low-dose range (0.02–1.0 μmol/kg) on the pharmacokinetics and biodistribution in rats, rabbits, and humans. The biodistribution and pharmacokinetics of 99mTc-PEG liposomes at various dose levels were studied in rats and rabbits with a focalEscherichia coli infection. Scintigraphic images were recorded on a gamma camera. In addition, the role of macrophages in the biodistribution of a low-dose PEG liposome injection was studied. Finally, the pharmacokinetics of 99mTc-PEG liposomes at two lipid dose levels was studied in four patients. At a dose level of 0.03 μmol/kg, the blood level in rats at 4 h postinjection was significantly lower than at the highest dose level (1.1 μmol/kg). The same effect was observed in rabbits where enhanced clearance was observed at a dose level of 0.02 μmol/kg. The circulatory half-life decreased from 10.4 to 3.5 h (at 1.0 and 0.02 μmol/kg, respectively). At the lowest dose level, liposomes were mainly taken up by the liver and to a lesser extent by the spleen. Injection of a low dose of PEG liposomes in macrophage-depleted rabbits resulted in normal pharmacokinetics, suggesting involvement of macrophages in the effectuation of the rapid elimination of the liposomes from the circulation. Most importantly, the rapid clearance of low-dose PEG liposomes was also observed in humans when relatively low lipid doses were administered. This study showed that at very low lipid doses the biodistribution of PEG liposomes is dramatically altered. The American Society for Pharmacology and Experimental Therapeutics