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

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 4.5g every 8h (q8h) or 6.75g 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 fAUC0–24≥96mgh/L was calculated for tazobactam. Mean±S.D. patient demographics were: age 49±10 years; weight 161±29kg; and body mass index 52.3±10.8kg/m2. For piperacillin and tazobactam, respectively, the mean±S.D. elimination rate was 0.440±0.177h−1 and 0.320±0.145h−1, volume of distribution was 33.4±14.0L (0.21±0.07L/kg) and 37.5±15.3L (0.23±0.08L/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≤16μg/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.