Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam administered by prolonged infusion in aged critically ill patients

Abstract

Objective To describe the plasma concentration-time profiles and to evaluate the pharmacokineties and pharmacodynamics of piperacillin/ tazobactam in hospitalised aged critically ill patients administered by prolonged infusion.Methods Five ICU patients received 4.5 g every 8 h (q8h),infused over 3 h.2 ml blood samples were collected at the time of 0 h,0.25 h,0.5 h,1 h,2 h,3 h,4 h,5 h,6 h,8 h,respectively,then centrifugated 10 minutes with 3 500 r/min.The supernatant.was extracted and stored at -23 ℃.Piperacillin and tazobactam concentrations in plasma were measured using ultra performance liquid chromatography tandem mass spectrometry,and pharmacokinetic parameters were determined by noncompartmental methods.Monte Carlo simulations (10 000 patients) were performed to calculate the probability of target attainment (PTA) at MIC ranging from 1 μg/ml to 64 μg/ml.The pharmacodynamic target was free piperacillin concentration remaining above the MIC for 50％ of the dosing interval.Results The maximum serum concentrations,half-life,volume of distribution and clearance of piperacillin were (97.64 ± 27.16) mg/L,(2.32 ± 0.81 ) h,(30.51 ± 15.2) L,(9.27 ± 2.69) L/h,respectively.In the Monte Carlo simulation study,the PTA was 100％ and 42.54％ at MIC≤16 μg/ml and 32 μg/ml,respectively.Conclusions This paper represents the population pharmacokinetics of piperacillin/tazobactam in aged critically ill patients in ICU.The data describe different pharmacokinetic parameters from those observed in other patient populations.The results of the Monte Carlo simulations suggest that piperacillin/tazobactam 4.5 g q8h infused over 3 h provides excellent target attainment for bacterial pathogens,especially at MIC≤16 μg/ml. Key words: Pharmacokinetics/pharmacodynamics; Monte Carlo simulation; Prolonged infusion therapy; Probability of target attainment