title: Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Yong Kyun
authors.identifier: http://orcid.org/0000-0002-7935-6952
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology, Inje University College of Medicine, Busan, Korea.
authors.forename: Jin Ah
authors.identifier: http://orcid.org/0000-0003-2439-377X
authors.initials: JA
authors.lastname: Jung
authors.affiliation: Department of Clinical Pharmacology, Inje University College of Medicine, Busan, Korea.
authors.forename: Hyang Ki
authors.initials: HK
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, School of Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Bae
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Korea.
authors.forename: Jian
authors.initials: J
authors.lastname: Hur
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Jin
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Shin Woo
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea.
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Kwon
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Internal Medicine, Cheongju St. Mary's Hospital, Cheongju, Korea.
authors.forename: Sang Rok
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology, Inje University College of Medicine, Busan, Korea.
authors.forename: Jae Gook
authors.initials: JG
authors.lastname: Shin
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea. smkimkor@yahoo.com.
authors.forename: Sungmin
authors.identifier: http://orcid.org/0000-0003-3518-966X
authors.initials: S
authors.lastname: Kiem
keywords: Clearance; Piperacillin; Population pharmacokinetics; Race; Tazobactam