Pharmacokinetic and pharmacodynamic evaluation of two dosing regimens for piperacillin-tazobactam

Pharmacotherapy. 2002 May;22(5):569-77. doi: 10.1592/phco.22.8.569.33209.


Study objective: To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin-tazobactam against commonly encountered pathogens. The regimens compared were piperacillin 4.0 g-tazobactam 0.5 g administered every 8 hours, and piperacillin 3.0 g-tazobactam 0.375 g administered every 6 hours.

Design: Multiple-dose, open-label, randomized, crossover study.

Setting: Clinical research center at Hartford Hospital.

Subjects: Twelve healthy volunteers.

Intervention: The two dosing regimens for piperacillin-tazobactam were administered intravenously in crossover design. Blood was sampled after the third dose.

Measurements and main results: Drug concentrations were determined by a validated high-performance liquid chromatography assay. The percentage of time above minimum inhibitory concentration (%T>MIC) for piperacillin was calculated for a range of MIC values. The maximum concentration (Cmax), area under the concentration-time curve (AUC0-tau), and total clearance of piperacillin differed significantly between the two study regimens, as did the Cmax, AUC0-tau, volume of distribution, and total clearance of tazobactam (p<0.05). The piperacillin 4.0 g-tazobactam 0.5 g regimen provided 40-50% T>MIC for MIC values 8-16 microg/ml; a similar value for the piperacillin 3.0 g-tazobactam 0.375 g regimen was 16-32 microg/ml.

Conclusion: Although statistically significant differences in the pharmacodynamic profile were noted for the regimens, both provide adequate T>MIC against commonly encountered pathogens considered susceptible to piperacillin-tazobactam. However, for treatment of Pseudomonas aeruginosa infection, combination therapy or higher-dosage regimens (e.g., piperacillin 3.0 g-tazobactam 0.375 g every 4 hours, piperacillin 4.0 g-tazobactam 0.5 g every 6 hours, or continuous-infusion piperacillin 12 g-tazobactam 1.5 g/day) may be a prudent option when full MIC data are unavailable.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Therapy, Combination / administration & dosage*
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / pharmacokinetics*
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacokinetics*
  • Female
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Male
  • Microbial Sensitivity Tests
  • Penicillanic Acid / administration & dosage*
  • Penicillanic Acid / adverse effects
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / pharmacokinetics*
  • Penicillins / administration & dosage*
  • Penicillins / adverse effects
  • Penicillins / pharmacokinetics*
  • Piperacillin / administration & dosage*
  • Piperacillin / adverse effects
  • Piperacillin / pharmacokinetics*
  • Tazobactam
  • beta-Lactamase Inhibitors*


  • Enzyme Inhibitors
  • Penicillins
  • beta-Lactamase Inhibitors
  • Penicillanic Acid
  • Tazobactam
  • Piperacillin