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

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 >120 kg received piperacillin/tazobactam 4.5 g every 8 h (q8h) or 6.75 g q8h infused over 4 h. 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 +/- 14.0 L (0.21 +/- 0.07 L/kg) and 37.5 +/- 15.3 L (0.23 +/- 0.08 L/kg), and systemic clearance was 13.7 +/- 5.2 L/h and 11.1 +/- 4.2 L/h. For piperacillin, the PTA was >= 91% for doses >= 4.5 g q8h at MICs <= 16 mu g/mL. For tazobactam, the PTA was 57%, 84% and 94% for doses of 4.5, 6.75 and 9.0 g q8h, respectively. The pharmacokinetics of piperacillin and tazobactam are altered in obese patients. To ensure adequate tazobactam concentrations for beta-lactamase inhibition, it may be prudent to employ larger initial doses for empirical therapy in obese patients. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.