Piperacillin pharmacokinetics in subjects with chronic renal failure

The pharmacokinetic parameters of piperacillin sodium were studied in eight volunteer subjects with chronic renal failure. Subjects were given a single 30-min intravenous infusion of 70 mg/kg (lean body weight) on their off-dialysis day. Blood was drawn from the contralateral arm at 15 and 30 min and 1, 3, 6, 9, and 12 h from the start of the infusion. Kinetic parameters were determined during the elimination phase with a one-compartment open model for linear kinetics. The following pharmacokinetic parameters (mean +/- standard deviation) were determined for the eight subjects: elimination half-life = 3.33 +/- 0.99 h, elimination rate constant = 0.22 +/- 0.06 h-1, apparent volume of distribution = 0.18 +/- 0.05 liters per kg, and total body clearance = 0.041 +/- 0.019 liters per kg/h. The mean peak serum concentration was 372 +/- 125 microgram/ml, and mean trough at 12 h was 39 +/- 27 microgram/ml. A dose of 70 mg/kg (lean body weight) or a dose of 4 g appears to provide adequate serum concentrations against susceptible organisms for a 12-h interval. No adverse reactions were noted in any subject throughout the study.