Piperacillin-tazobactam pharmacokinetics in patients with intraabdominal infections
Jhee, S.S.; Kern, J.W.; Burm, J.P.; Yellin, A.E.; Gill, M.A.
PharmacoTherapy 15(4): 472-478
1995
ISSN/ISBN: 0277-0008 PMID: 7479200 Document Number: 444357
Study Objective: To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam. Design: Sequential selection of patients entered into a randomized, open-label clinical efficacy trial. Setting: Los Angeles County-University of Southern California Medical Center. Participants: Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial. Interventions: Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours. Measurements and Main Results: The estimated noncompartmental pharmacokinetic parameters (mean +- SD) for piperacillin and tazobactam, respectively, were as follows: maximum 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; 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 cntdot hr/L and 36.3 +- 9.55 mg cntdot 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. Conclusion: 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.