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.
Vadiei
K
K
College of Pharmacy, University of Houston.
Lopez-Berestein
G
G
Perez-Soler
R
R
Luke
D R
DR
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