Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections
Polymyxin B is used as a last therapeutic option for the treatment of multidrug-resistant Gram-negative bacterial infections. This study aimed to develop a population pharmacokinetic model and limited sampling strategy, a method to estimate the area under the concentration curve (AUC) by using a lim...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2020-06-01
|
Series: | Frontiers in Pharmacology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00829/full |
id |
doaj-8659476cd8ae4e15bf21c5a04cea4664 |
---|---|
record_format |
Article |
spelling |
doaj-8659476cd8ae4e15bf21c5a04cea46642020-11-25T04:01:40ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-06-011110.3389/fphar.2020.00829543132Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial InfectionsPeile Wang0Peile Wang1Qiwen Zhang2Qiwen Zhang3Zhenfeng Zhu4Zhenfeng Zhu5Min Feng6Tongwen Sun7Jing Yang8Jing Yang9Xiaojian Zhang10Xiaojian Zhang11Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of ICU, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of General ICU, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaPolymyxin B is used as a last therapeutic option for the treatment of multidrug-resistant Gram-negative bacterial infections. This study aimed to develop a population pharmacokinetic model and limited sampling strategy, a method to estimate the area under the concentration curve (AUC) by using a limited number of samples, to assist therapeutic drug monitoring of polymyxin B in Chinese patients. Population pharmacokinetic analysis was performed using Phoenix® NLME with data obtained from 46 adult patients at steady state. Various demographic variables were investigated as potential covariates for population pharmacokinetic modeling. The limited sampling strategies based on the Bayesian approach and multiple linear regression were validated using the intraclass correlation coefficient and Bland-Altman analysis. As a result, the data was described by a two-compartment population pharmacokinetic model. Through the modeling, creatinine clearance was found to be a statistically significant covariate influencing polymyxin B clearance. The limited sampling strategies showed the two-point model (C0h and C2h) could predict polymyxin B exposure with good linear relativity (r2 > 0.98), and the four-point model (C1h, C1.5h, C4h, and C8h) performed best in predicting polymyxin B AUC (r2 > 0.99). In conclusion, this study successfully developed a population pharmacokinetic model and limited sampling strategies that could be applied in clinical practice to assist in therapeutic drug monitoring of polymyxin B in Chinese patients.https://www.frontiersin.org/article/10.3389/fphar.2020.00829/fullpolymyxin Bpopulation pharmacokineticslimited sampling strategytherapeutic drug monitoringmultidrug-resistant Gram-negative bacterial infection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peile Wang Peile Wang Qiwen Zhang Qiwen Zhang Zhenfeng Zhu Zhenfeng Zhu Min Feng Tongwen Sun Jing Yang Jing Yang Xiaojian Zhang Xiaojian Zhang |
spellingShingle |
Peile Wang Peile Wang Qiwen Zhang Qiwen Zhang Zhenfeng Zhu Zhenfeng Zhu Min Feng Tongwen Sun Jing Yang Jing Yang Xiaojian Zhang Xiaojian Zhang Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections Frontiers in Pharmacology polymyxin B population pharmacokinetics limited sampling strategy therapeutic drug monitoring multidrug-resistant Gram-negative bacterial infection |
author_facet |
Peile Wang Peile Wang Qiwen Zhang Qiwen Zhang Zhenfeng Zhu Zhenfeng Zhu Min Feng Tongwen Sun Jing Yang Jing Yang Xiaojian Zhang Xiaojian Zhang |
author_sort |
Peile Wang |
title |
Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections |
title_short |
Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections |
title_full |
Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections |
title_fullStr |
Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections |
title_full_unstemmed |
Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections |
title_sort |
population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of polymyxin b in chinese patients with multidrug-resistant gram-negative bacterial infections |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-06-01 |
description |
Polymyxin B is used as a last therapeutic option for the treatment of multidrug-resistant Gram-negative bacterial infections. This study aimed to develop a population pharmacokinetic model and limited sampling strategy, a method to estimate the area under the concentration curve (AUC) by using a limited number of samples, to assist therapeutic drug monitoring of polymyxin B in Chinese patients. Population pharmacokinetic analysis was performed using Phoenix® NLME with data obtained from 46 adult patients at steady state. Various demographic variables were investigated as potential covariates for population pharmacokinetic modeling. The limited sampling strategies based on the Bayesian approach and multiple linear regression were validated using the intraclass correlation coefficient and Bland-Altman analysis. As a result, the data was described by a two-compartment population pharmacokinetic model. Through the modeling, creatinine clearance was found to be a statistically significant covariate influencing polymyxin B clearance. The limited sampling strategies showed the two-point model (C0h and C2h) could predict polymyxin B exposure with good linear relativity (r2 > 0.98), and the four-point model (C1h, C1.5h, C4h, and C8h) performed best in predicting polymyxin B AUC (r2 > 0.99). In conclusion, this study successfully developed a population pharmacokinetic model and limited sampling strategies that could be applied in clinical practice to assist in therapeutic drug monitoring of polymyxin B in Chinese patients. |
topic |
polymyxin B population pharmacokinetics limited sampling strategy therapeutic drug monitoring multidrug-resistant Gram-negative bacterial infection |
url |
https://www.frontiersin.org/article/10.3389/fphar.2020.00829/full |
work_keys_str_mv |
AT peilewang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT peilewang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT qiwenzhang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT qiwenzhang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT zhenfengzhu populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT zhenfengzhu populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT minfeng populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT tongwensun populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT jingyang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT jingyang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT xiaojianzhang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections AT xiaojianzhang populationpharmacokineticsandlimitedsamplingstrategyfortherapeuticdrugmonitoringofpolymyxinbinchinesepatientswithmultidrugresistantgramnegativebacterialinfections |
_version_ |
1724445789933010944 |