Steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients

Int J Antimicrob Agents. 2013 Jan;41(1):52-6. doi: 10.1016/j.ijantimicag.2012.09.004. Epub 2012 Dec 8.

Abstract

The study objective was to evaluate steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients. Fourteen hospitalised patients weighing >120kg received piperacillin/tazobactam 4.5 g every 8 h (q8h) or 6.75 g q8h infused over 4h. Blood samples were collected at steady-state and drug concentrations were determined. Pharmacokinetic parameters were estimated and 5000-patient Monte Carlo simulations were performed for four prolonged-infusion dosing regimens. The probability of target attainment (PTA) for ≥50% fT>MIC was calculated for piperacillin at various MICs, and the PTA for fAUC(0-24)≥96 mg h/L was calculated for tazobactam. Mean±S.D. patient demographics were: age 49±10 years; weight 161±29 kg; and body mass index 52.3±10.8 kg/m(2). For piperacillin and tazobactam, respectively, the mean±S.D. elimination rate was 0.440±0.177 h(-1) and 0.320±0.145 h(-1), volume of distribution was 33.4±14.0L (0.21±0.07L/kg) and 37.5±15.3L (0.23±0.08 L/kg), and systemic clearance was 13.7±5.2L/h and 11.1±4.2L/h. For piperacillin, the PTA was ≥91% for doses ≥4.5g q8h at MICs≤16 μg/mL. For tazobactam, the PTA was 57%, 84% and 94% for doses of 4.5, 6.75 and 9.0g q8h, respectively. The pharmacokinetics of piperacillin and tazobactam are altered in obese patients. To ensure adequate tazobactam concentrations for β-lactamase inhibition, it may be prudent to employ larger initial doses for empirical therapy in obese patients.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Blood Chemical Analysis
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Obesity
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacokinetics
  • Piperacillin / administration & dosage
  • Piperacillin / pharmacokinetics
  • Piperacillin, Tazobactam Drug Combination
  • Time Factors

Substances

  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Piperacillin