Abstract: | Dogs and rats were studied to evaluate the excretion of two new acyl-ureidopenicillins, azlocillin and mezlocillin, in the pancreatic fluid. After intravenous administration of 55 mg X kg-1 of either drug, an extremely low concentration (less than 3.0 micrograms X ml-1) of both antibiotics was measured in pancreatic juice of conscious dogs. In rats, both azlocillin and mezlocillin were excreted by the pancreas in bactericidal concentrations (greater than 10 micrograms X ml-1) during the first 15 min following their injection. In anesthetized dogs and rats in which acute pancreatitis was induced by injection of sodium taurocholate into the main pancreatic duct, the tissue concentration of mezlocillin (55 mg X kg-1 i.v.) was significantly higher than in the pancreatic tissue of control animals. In both instances, bactericidal concentrations of mezlocillin were measured in the pancreatic tissue. During the first 30 min following its injection, the concentration of mezlocillin was about five times higher in inflammed pancreatic tissue than in the normal pancreas (dogs: 44 +/- 14 vs. 5 +/- 3 micrograms X g-1 tissue; rats: 67 +/- 10 vs. 13 +/- 2 micrograms X g-1). These data indicate that (1) azlocillin and mezlocillin are excreted in bactericidal concentrations by the normal pancreas only in rats but not in dogs, and (2) in both species, bactericidal concentrations of mezlocillin can be observed in the normal pancreatic tissue and in acute pancreatitis; its concentration being significantly higher in acute pancreatitis than in controls. |