Tissue distribution and in vivo immunosuppressive activity of liposomal cyclosporine.
The distribution and immunosuppressive activity of liposomal cyclosporine (L-CSA) when administered iv as single- and multiple-doses were compared with the commercially available cyclosporine (C-CSA) in rats. CSA concentrations in the spleen and liver were significantly greater 1 hr after dosing in rats given L-CSA compared with C-CSA. The apparent tissue to blood partition coefficient at 1 hr after dosing was significantly greater for the liver and spleen of rats treated with L-CSA compared with C-CSA. Drug concentrations 24 hr after single doses of L-CSA were significantly lower in the kidney, heart, lung, and adipose tissues compared with animals given C-CSA. Lymphocyte-blastogenic response was studied in a separate group of rats given 10 mg/kg/day of L-CSA or C-CSA for 10 days compared with drug-free control groups. A 3-fold decrease in blastogenic response was observed in rats given L-CSA compared with C-CSA-treated rats (12.7 +/- 11.8 vs. 34.9 +/- 11.3 x 10(3) dpm/10(6) cells; p less than 0.05). These data suggest that the liposomal formulation of CSA leads to enhanced tissue levels of CSA in the spleen coupled with augmentation in immunosuppressive activity.
College of Pharmacy, University of Houston.
K
K
Vadiei
G
G
Lopez-Berestein
R
R
Perez-Soler
D R
DR
Luke
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004337:Drug Carriers; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D016572:Cyclosporine