Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep;48(3):209-215.
doi: 10.3947/ic.2016.48.3.209. Epub 2016 Sep 6.

Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections

Yong Kyun Kim  1 , Jin Ah Jung  2 , Hyang Ki Choi  2 , In Gyu Bae  3 , Won Suk Choi  4 , Jian Hur  5 , Sung Joon Jin  6 , Shin Woo Kim  7 , Ki Tae Kwon  8 , Sang Rok Lee  9 , Jae Gook Shin  2 , Sungmin Kiem  10 ; Pharmacokinetics-Pharmacodynamics of Antibiotics Working Group under Korean Society for Chemotherapy
Affiliations

Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections

Yong Kyun Kim et al. Infect Chemother. 2016 Sep.

Abstract

Background: For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients' characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections.

Materials and methods: At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CL(cr)) ≤50 ml/min or CL(cr) >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P < 0.05 for selection and P < 0.01 for elimination.

Results: Both piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CL(cr) /47 for piperacillin and CL = 1.76 + 4.81 × CL(cr) /47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam.

Conclusion: The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance.

Keywords: Clearance; Piperacillin; Population pharmacokinetics; Race; Tazobactam.

PubMed Disclaimer

Conflict of interest statement

The study drug was provided by the Kuhnil Pharmaceutical Company.

Figures

Figure 1
Figure 1
Goodness of fit plots for the final pharmacokinetic models for piperacillin (4 figures of the upper panel) and tazobactam (4 figures of the lower panel). The grey line indicates the line of identity; the red line indicates the linear regression line. CWRES: conditional weighted residual.
Figure 2
Figure 2
Visual predictive check for the final piperacillin pharmacokinetic model, simulation of 2,000 data sets, using the final pharmacokinetic parameter estimates. Open circles indicate observed concentrations; the red full line indicates the median value; the lower and upper red dotted lines indicate the 2.5th and 97.5th predicted value, respectively.
See this image and copyright information in PMC

References

    1. Gin A, Dilay L, Karlowsky JA, Walkty A, Rubinstein E, Zhanel GG. Piperacilin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther. 2007;5:365–383. - PubMed
    1. Maltezou HC, Nikolaidis P, Lebesii E, Dimitriou L, Androulakakis E, Kafetzis DA. Piperacillin/tazobactam versus cefotaxime plus metronidazole for treatment of children with intra-abdominal infections requiring surgery. Eur J Clin Microbiol Infect Dis. 2001;20:643–646. - PubMed
    1. Tumbarello M, Sanguinetti M, Montuori E, Trecarichi EM, Posteraro B, Fiori B, Citton R, D’Inzeo T, Fadda G, Cauda R, Spanu T. Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment. Antimicrob Agents Chemother. 2007;51:1987–1994. - PMC - PubMed
    1. Peralta G, Lamelo M, Alvarez-García P, Velasco M, Delgado A, Horcajada JP, Montero M, Roiz MP, Fariñas MC, Alonso J, Martínez LM, Gutiérrez-Macías A, Alava JA, Rodríguez A, Fleites A, Navarro V, Sirvent E, Capdevila JA, SEMI- BLEE STUDY GROUP Impact of empirical treatment in extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp bacteremia. A multicentric cohort study. BMC Infect Dis. 2012;12:245. - PMC - PubMed
    1. Turnidge JD. The pharmacodynamics of β-lactams. Clin Infect Dis. 1998;27:10–22. - PubMed