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Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients

Currently, polymyxin B has been widely used in the treatment of multidrug-resistant Gram-negative pathogen infections. Due to the limited pharmacokinetic/pharmacodynamic data, the optimal dosage regimen for the recently proposed therapeutic target of the area under the concentration-time curve over...

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Autores principales: Li, Ying, Deng, Yang, Zhu, Zhen-Yu, Liu, Yi-Ping, Xu, Ping, Li, Xin, Xie, Yue-Liang, Yao, Heng-Chang, Yang, Liu, Zhang, Bi-Kui, Zhou, Yan-Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424097/
https://www.ncbi.nlm.nih.gov/pubmed/34512352
http://dx.doi.org/10.3389/fphar.2021.727170
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author Li, Ying
Deng, Yang
Zhu, Zhen-Yu
Liu, Yi-Ping
Xu, Ping
Li, Xin
Xie, Yue-Liang
Yao, Heng-Chang
Yang, Liu
Zhang, Bi-Kui
Zhou, Yan-Gang
author_facet Li, Ying
Deng, Yang
Zhu, Zhen-Yu
Liu, Yi-Ping
Xu, Ping
Li, Xin
Xie, Yue-Liang
Yao, Heng-Chang
Yang, Liu
Zhang, Bi-Kui
Zhou, Yan-Gang
author_sort Li, Ying
collection PubMed
description Currently, polymyxin B has been widely used in the treatment of multidrug-resistant Gram-negative pathogen infections. Due to the limited pharmacokinetic/pharmacodynamic data, the optimal dosage regimen for the recently proposed therapeutic target of the area under the concentration-time curve over 24 h in steady state divided by the minimum inhibitory concentration 50–100 mg⋅h/L has not yet been established. Moreover, most studies have focused on critically ill patients, yet there have been no studies in the field of renal transplantation. To optimize the dosage strategy and reduce the risk of toxicity, a population pharmacokinetics model of polymyxin B with the Phoenix NLME program was developed in our study. A total of 151 plasma samples from 50 patients were collected in the present study. Polymyxin B plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. A one-compartment model adequately described the data, and the clearance and volume of distribution were 1.18 L/h and 12.09 L, respectively. A larger creatinine clearance was associated with increased clearance of polymyxin B (p < 0.01). Monte Carlo simulation showed that a regimen of a 75 mg loading dose with a 50 mg maintenance dose was a better option to achieve an optimal therapeutic effect (minimum inhibitory concentration ≤1 mg/L) and to reduce the incidence of side effects for patients with renal impairments. The developed model suggested that dosing adjustment should be based on renal function in renal transplant patients.
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spelling pubmed-84240972021-09-09 Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients Li, Ying Deng, Yang Zhu, Zhen-Yu Liu, Yi-Ping Xu, Ping Li, Xin Xie, Yue-Liang Yao, Heng-Chang Yang, Liu Zhang, Bi-Kui Zhou, Yan-Gang Front Pharmacol Pharmacology Currently, polymyxin B has been widely used in the treatment of multidrug-resistant Gram-negative pathogen infections. Due to the limited pharmacokinetic/pharmacodynamic data, the optimal dosage regimen for the recently proposed therapeutic target of the area under the concentration-time curve over 24 h in steady state divided by the minimum inhibitory concentration 50–100 mg⋅h/L has not yet been established. Moreover, most studies have focused on critically ill patients, yet there have been no studies in the field of renal transplantation. To optimize the dosage strategy and reduce the risk of toxicity, a population pharmacokinetics model of polymyxin B with the Phoenix NLME program was developed in our study. A total of 151 plasma samples from 50 patients were collected in the present study. Polymyxin B plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. A one-compartment model adequately described the data, and the clearance and volume of distribution were 1.18 L/h and 12.09 L, respectively. A larger creatinine clearance was associated with increased clearance of polymyxin B (p < 0.01). Monte Carlo simulation showed that a regimen of a 75 mg loading dose with a 50 mg maintenance dose was a better option to achieve an optimal therapeutic effect (minimum inhibitory concentration ≤1 mg/L) and to reduce the incidence of side effects for patients with renal impairments. The developed model suggested that dosing adjustment should be based on renal function in renal transplant patients. Frontiers Media S.A. 2021-08-25 /pmc/articles/PMC8424097/ /pubmed/34512352 http://dx.doi.org/10.3389/fphar.2021.727170 Text en Copyright © 2021 Li, Deng, Zhu, Liu, Xu, Li, Xie, Yao, Yang, Zhang and Zhou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Ying
Deng, Yang
Zhu, Zhen-Yu
Liu, Yi-Ping
Xu, Ping
Li, Xin
Xie, Yue-Liang
Yao, Heng-Chang
Yang, Liu
Zhang, Bi-Kui
Zhou, Yan-Gang
Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients
title Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients
title_full Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients
title_fullStr Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients
title_full_unstemmed Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients
title_short Population Pharmacokinetics of Polymyxin B and Dosage Optimization in Renal Transplant Patients
title_sort population pharmacokinetics of polymyxin b and dosage optimization in renal transplant patients
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424097/
https://www.ncbi.nlm.nih.gov/pubmed/34512352
http://dx.doi.org/10.3389/fphar.2021.727170
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