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

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...

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Autores principales: Kim, Yong Kyun, Jung, Jin Ah, Choi, Hyang-Ki, Bae, In-Gyu, Choi, Won Suk, Hur, Jian, Jin, Sung Joon, Kim, Shin-Woo, Kwon, Ki Tae, Lee, Sang-Rok, Shin, Jae-Gook, Kiem, Sungmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Infectious Diseases and Korean Society for Chemotherapy 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048002/
https://www.ncbi.nlm.nih.gov/pubmed/27659435
http://dx.doi.org/10.3947/ic.2016.48.3.209
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author Kim, Yong Kyun
Jung, Jin Ah
Choi, Hyang-Ki
Bae, In-Gyu
Choi, Won Suk
Hur, Jian
Jin, Sung Joon
Kim, Shin-Woo
Kwon, Ki Tae
Lee, Sang-Rok
Shin, Jae-Gook
Kiem, Sungmin
author_facet Kim, Yong Kyun
Jung, Jin Ah
Choi, Hyang-Ki
Bae, In-Gyu
Choi, Won Suk
Hur, Jian
Jin, Sung Joon
Kim, Shin-Woo
Kwon, Ki Tae
Lee, Sang-Rok
Shin, Jae-Gook
Kiem, Sungmin
author_sort Kim, Yong Kyun
collection PubMed
description 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.
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spelling pubmed-50480022016-10-04 Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections  Kim, Yong Kyun Jung, Jin Ah Choi, Hyang-Ki Bae, In-Gyu Choi, Won Suk Hur, Jian Jin, Sung Joon Kim, Shin-Woo Kwon, Ki Tae Lee, Sang-Rok Shin, Jae-Gook Kiem, Sungmin Infect Chemother Original Article 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. The Korean Society of Infectious Diseases and Korean Society for Chemotherapy 2016-09 2016-09-06 /pmc/articles/PMC5048002/ /pubmed/27659435 http://dx.doi.org/10.3947/ic.2016.48.3.209 Text en Copyright © 2016 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kim, Yong Kyun
Jung, Jin Ah
Choi, Hyang-Ki
Bae, In-Gyu
Choi, Won Suk
Hur, Jian
Jin, Sung Joon
Kim, Shin-Woo
Kwon, Ki Tae
Lee, Sang-Rok
Shin, Jae-Gook
Kiem, Sungmin
Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections 
title Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections 
title_full Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections 
title_fullStr Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections 
title_full_unstemmed Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections 
title_short Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections 
title_sort population pharmacokinetic analysis of piperacillin/tazobactam in korean patients with acute infections 
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048002/
https://www.ncbi.nlm.nih.gov/pubmed/27659435
http://dx.doi.org/10.3947/ic.2016.48.3.209
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