Pharmacologic and Toxicologic Studies with the Polymyxins. II. Comparative Pharmacologic Studies of the Sulfate and Methanesulfonate Salts of Polymyxin B and Colistin in Dogs

The sulfate and methanesulfonate salts of polymyxin B and colistin exhibited important pharmacologic differences. The sulfate salts disappeared from plasma at a slower rate following intramuscular administration, were excreted at a much slower rate in the urine and showed a far greater calculated volume percent distribution. It is felt that these differences can be explained largely on the basis of their far greater degree of binding to plasma proteins and tissues. Evidence is presented that colistin is metabolized by the dog and that the site of metabolism may be the kidney. Renal clearance studies indicate that glomerular filtration is the mechanism of urinary excretion of colistin methanesulfonate.