Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease.
Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase-producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended.
Johnson
C A
CA
University of Wisconsin Hospital and Clinics, Madison.
Halstenson
C E
CE
Kelloway
J S
JS
Shapiro
B E
BE
Zimmerman
S W
SW
Tonelli
A
A
Faulkner
R
R
Dutta
A
A
Haynes
J
J
Greene
D S
DS
D000328:Adult; D003401:Creatine / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000009:adverse effects / Q000493:pharmacokinetics*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010878:Piperacillin / Q000009:adverse effects / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D000078142:Tazobactam; D013997:Time Factors; D065093:beta-Lactamase Inhibitors
D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D003401:Creatine; D000078142:Tazobactam; D010878:Piperacillin