PIPERACILLIN-TAZOBACTAM PHARMACOKINETICS IN PATIENTS WITH INTRAABDOMINAL INFECTIONS

Study Objective, To determine the appropriate compartmental and noncom partmental pharmacokinetic parameters for intravenous piperacillin and tazobactam. Design, Sequential selection of patients entered into a r andomized, open-label clinical efficacy trial. Setting, Los Angeles Co unty-University of Southern California Medical Center. Participants. S equential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial, Interventions. Pat ients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours. Measurements and Main Results. Th e estimated noncompartmental pharmacokinetic parameters (mean +/- SD) for piperacillin and tazobactam, respectively, were as follows: maximu m concentration in plasma 218.7 +/- 48.9 mu g/ml and 27.8 +/- 9.1 mu g /ml; half-life 1.07 +/- 0.22 hours and 1.00 +/- 0.27 hours; eliminatio n rate constant 0.67 +/- 0.13 hr(-1) and 0.73 +/- 0.18 hr(-1); area un der 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 stea dy state 21.00 +/- 4.18 L and 22.47 +/- 8.27 L; and mean residence tim e 1.72 +/- 0.29 hours and 1.79 +/- 0.35 hours. Conclusion. Our finding s were similar to those in other surgical patient models. The two-comp artmental model best described piperacillin and tazobactam disposition in our patients. Bayesian analyses of the two-compartment models of p iperacillin and tazobactam were able to predict trough, peak, and 2-ho ur postadministration levels without bias.