Selected tissue distribution of liposomal methylprednisolone in rats.
The distribution of methylprednisolone (MPL) in various rat tissues following 2 mg/kg IV bolus doses of liposomal drug (L-MPL) and drug in solution was investigated. Animals were sacrificed at selected times post-dosing until 120 h. Liver, spleen, thymus, heart, lungs, muscle, kidney and brain were excised and the concentrations of MPL were measured using HPLC after homogenizing organs in buffer. The incorporation of MPL in liposomes did not alter the uptake of drug by heart, lung and muscle. Drug concentrations in brain were undetectable. In the kidney the MPL concentrations after 1 h were higher for liposomal drug and not detectable at later time points. Tissue to plasma partition coefficients were close to unity in lung, heart, and muscle at 1-2 h after the dose of drug in solution and increased by 7.5 times for spleen and 6 times for thymus after the dose of L-MPL. There were no significant differences between the weights of organs expressed in percent of body weight. These results demonstrate that, while the sequestration of L-MPL by lymphatic tissues occurred, the uptake of drug by the other tissues did not increase. This may be beneficial for preferential targeting of the immune system.
Mishina
E V
EV
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, NY 14260.
Jusko
W J
WJ
D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D008775:Methylprednisolone