INTERACTION OF SWAINSONINE WITH LYMPHOID AND HIGHLY PERFUSED TISSUES - A PHARMACOKINETICS EXPLANATION FOR SUSTAINED IMMUNOMODULATION

The kinetics of inhibition of metastasis by the immunomodulator swains onine (SW) is effective 1 to 3 days after administration It is likely that SW's prolonged antimetastatic effect is due to its mitogenic prop erty (spleenocytes isolated from animals treated with SW for 42 - 72 h ours stimulated DNA synthesis that remained elevated for up to 3 days after removal of the drug from the drinking water). An analysis of SW in lymphoid (spleen and thymus) and highly perfused tissues was undert aken to determine if SW's sustained antimetastatic effect could be cor related to its retention. C57BL/6 mice received [H-3]SW in drinking wa ter for 24 - 72 hours and thereafter, received SW-free drinking for 24 , 48, and 72 hours. Lymphoid and highly perfused tissues were analyzed for [H-3]SW. At 24, 48, and 72 hours, spleen SW levels are, respectiv ely, at least 2.33, 2.25, and 2.00 times greater than the perfused tis sue; and thymus are, respectively, 1.44, 1.50, and 1.77 as great as th e perfused tissue (kidney) with the highest SW level. These studies su ggest that SW is predominantly retained for at least 72 hours, in lymp hoid tissue. The targeting and retention of SW for lymphoid tissue day s after removal of SW fi om animal drinking water is consistent with a ) the immunomodulatory/mitogenic property and b) the sustained antimet astatic effect attributed to SW.