Ampicillin and sulbactam pharmacokinetics and pharmacodynamics in continuous ambulatory peritoneal dialysis (CAPD)

Abstract

The fixed combination antibiotic ampicillin/sulbactam may provide a new, safe, and effective method of treating dialysis-related bacterial peritonitis. The pharmacokinetics of this antibiotic combination were determined in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The pharmacodynamic activity of this drug was also determined by use of mean bactericidal titers against selected bacterial strains. Six noninfected CAPD patients in a randomized two-way crossover study were given a fixed dose of ampicillin (2 gm) and sulbactam (1 gm) either intravenously or intraperitoneally. The mean peak ampicillin and sulbactam serum concentrations following intravenous dosing were 170.3 and 87.5 micrograms/mL, respectively. The mean peak serum concentrations of ampicillin and sulbactam following intraperitoneal dosing were 48.0 and 27.8 micrograms/mL, respectively. Absolute bioavailabilities of the intraperitoneal ampicillin and sulbactam doses were 60% and 68%. Both drugs exhibited similar distribution and elimination characteristics. Renal failure markedly reduced drug elimination. Intraperitoneal administration of ampicillin/sulbactam provided satisfactory inhibitory and bactericidal antibiotic titers for most organisms in dialysate at 6 h but not 24 h. Ampicillin/sulbactam (2 gm/1 gm) should be administered every 12 h to patients with peritoneal dialysis-related peritonitis.