Piperacillin-tazobactam pharmacokinetics in patients with intraabdominal infections.
OBJECTIVE
To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam.


METHODS
Sequential selection of patients entered into a randomized, open-label clinical efficacy trial.


METHODS
Los Angeles County-University of Southern California Medical Center.


METHODS
Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial.


METHODS
Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours.


RESULTS
The estimated noncompartmental pharmacokinetic parameters (mean +/- SD) for piperacillin and tazobactam, respectively, were as follows: maximum concentration in plasma 218.7 +/- 48.9 micrograms/ml and 27.8 +/- 9.1 micrograms/ml; half-life 1.07 +/- 0.22 hours and 1.00 +/- 0.27 hours; elimination rate constant 0.67 +/- 0.13 hr-1 and 0.73 +/- 0.18 hr-1; area under the concentration-time curve from zero hour to infinity 288.5 +/- 71.25 mg.hr/L and 36.3 +/- 9.55 mg.hr/L; total plasma clearance 14.75 +/- 3.93 L/hour and 14.78 +/- 4.39 L/hour; renal clearance 5.69 +/- 1.94 L/hour and 7.85 +/- 3.37 L/hour; volume of distribution at steady state 21.00 +/- 4.18 L and 22.47 +/- 8.27 L; and mean residence time 1.72 +/- 0.29 hours and 1.79 +/- 0.35 hours.


CONCLUSIONS
Our findings were similar to those in other surgical patient models. The two-compartmental model best described piperacillin and tazobactam disposition in our patients. Bayesian analyses of the two-compartment models of piperacillin and tazobactam were able to predict trough, peak, and 2-hour postadministration levels without bias.
D000005:Abdomen / Q000382:microbiology*; D000293:Adolescent; D000328:Adult; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D015377:Cilastatin / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D015377:Cilastatin; D015378:Imipenem; D010397:Penicillanic Acid; D000077728:Cilastatin, Imipenem Drug Combination; D000078142:Tazobactam; D010878:Piperacillin