Abstract

The distribution, binding and in vivo antimicrobial activity of tritiated polymyxin B has been investigated in the mouse. The kidney was found to accumulate the radioactivity rapidly and to retain substantial quantities of the drug (>50 µg/g tissue) 168 hours after administration. On the other hand, the antibacterial activity of this tissue fell to one-half its peak level within four hours after injection. Most of the radioactivity was attached to particulate material in the cell homogenate, particularly to the 600 x g pellet. Attempts to displace the radioactive material from the kidney by subsequent treatment with unlabeled polymyxin B were unsuccessful. However, prior administration of unlabeled polymyxin B did markedly decrease the amount of radioactivity that accumulated in the kidney. Prior administration of cysteine, DL-methionine or glutathione also decreased the accumulation of radioactivity. The possible nature of the polymyxin B binding site is discussed in light of these findings and those of other workers.