SELECTED TISSUE DISTRIBUTION OF LIPOSOMAL METHYLPREDNISOLONE IN RATS

The distribution of methylprednisolone (MPL) in various rat tissues fo llowing 2 mg/kg IV bolus doses of liposomai drug (L-MPL) and drug in s olution was investigated. Animals were sacrificed at selected times po st-dosing until 120 h. Liver, spleen, thymus, heart, lungs, muscle, ki dney and brain were excised and the concentrations of MPL were measure d 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 no t detectable at later time points. Tissue to plasma partition coeffici ents 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 di fferences between the weights of organs expressed in precent of body w eight. These results demonstrate that, while the sequestration of L-MP L by lymphatic tissues occurred, the uptake of drug by the other tissu es did not increase. This may be beneficial for preferential targeting of the immune system.