DYNAMICS OF BINDING AND RELEASE OF THE POLYMYXIN ANTIBIOTICS BY TISSUES

¹ Madison Veterans Administration Hospital and the Department of Medicine, University of Wisconsin School of Medicine, Madison, Wisconsin

Binding and release of polymyxin B and colistimethate by tissues were studied in relation to toxicity by giving repeated injections to rabbits and measuring accumulation in serum and free and bound forms in tissue. Microbiologic assays were adjusted to take into account alteration of the slope and activity of each drug in serum and tissue extracts. Bound drug is probably not released from tissues in pure form but, rather, in partial association with membrane receptors. Free drug in tissue appears from assay characteristics to resemble closely the original antibiotic given to time animal. Binding sites appear to become saturated, except in the case of liver, as dosage is increased. Toxicity appeared after saturation of tissue binding sites. Time major difference between polymyxin B and colistimethate is in the tendency for polymyxin B to maintain much higher levels of free drug in all tissues. Both forms of tissue-associated antibiotics are released slowly from binding sites and persist as long as five days after the the last injection.