Pharmacokinetic of piperacillin/tazobactam in patients with sepsis during continuous venovenous hemodiafiltration

doi:10.12092/j.issn.1009-2501.2018.08.011

Abstract

Abstract:

AIM: To evaluate the pharmacokinetic of piperacillin/tazobactam in patients with sepsis during continuous venovenous hemodiafiltration and to analyse the influencing factors. METHODS: The patients with sepsis requiring CRRT in the intensive care units in a general hospital during June 2014 to May 2016 were enrolled as the subjects. First dose of piperacillin-tazobactam（4.5 g） was administered intravenously over 30 min. Blood samples were taken at 0, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480 min after infusion.The concentrations of piperacillin and tazobactam were determined by high-performance liquid chromatography（HPLC）, PK analysis was conducted using a non-compartmental approach, the DAS 3.2.1 software was used to calculate pharmacokinetic parameters, Linear regression analysis was used to analyze the relationship between patient characteristics/CRRT parameters and pharmacokinetics.Blood concentration maintained above the minimum inhibitory concentration (MIC) for 50%(f%T_＞MIC＞50%) as a pharmacodynamic target. RESULTS: Eight patients with sepsis receiving CVVHDF were included in the investigation. The maximum concentration (C _max) of piperacillin and tazobactam was 116.11（98.03-152.29）and 21.60（15.9-29.69）mg/L,respectively; The volume of distribution (V_d) was 1.05（0.70-1.56）and 0.69（0.56-0.78）L/kg, respectively; The elimination half-time (t_1/2) was 4.79（3.30-8.27）and 4.38（3.35-5.52）h, respectively; The total clearance rate (CL) was 7.67（5.66-9.71）and 6.11（4.36-10.03）L/h, respectively. In the multivariate analysis, the most significant factor associated with Cmax of piperacillin was replacement flow rate (β：-0.854，95%CI：-0.148--0.036，P=0.007), the most significant factor associated with CL of piperacillin was effluent flow rate（β：0.883，95%CI：0.133-0.433，P=0.004）.When MIC≤16 mg/L, all patients reached pharmacodynamic target, when 16 mg/L＜MIC＜32 mg/L, just 5 patients (62.5%) reached the target, while MIC≥64 mg /L, no patient reached the target. CONCLUSION: Both piperacillin and tazobactam for patients with sepsis receiving CVVHDF show significantly lower C _max, significantly longer t_1/2, and decreased CL. CL and t_1/2 remain consistent. When germ's MIC＞32 mg/L, the first dosage of 4.5 g piperacillin/ tazobactam may be not enough.

Key words: sepsis, continuous venovenous hemodiafiltration, piperacillin/tazobactam, high-performance liquid chromatography, pharmacokinetics

CLC Number:

R969.1

CAI Yun, XU Jinlong, ZHANG Mao. Pharmacokinetic of piperacillin/tazobactam in patients with sepsis during continuous venovenous hemodiafiltration[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(8): 905-911.

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