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Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients

The purposes of this study were to identify physiological and genetic factors that contributed to variability of pemetrexed (PEM) exposure and to optimize the dosing regimens for Chinese non-small cell lung carcinoma patients. A prospective population pharmacokinetics (PPK) research was performed in...

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Autores principales: Cao, Peng, Guo, Wei, Wang, Jun, Wu, Sanlan, Huang, Yifei, Wang, Yang, Liu, Yani, Zhang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9466465/
https://www.ncbi.nlm.nih.gov/pubmed/36105185
http://dx.doi.org/10.3389/fphar.2022.954242
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author Cao, Peng
Guo, Wei
Wang, Jun
Wu, Sanlan
Huang, Yifei
Wang, Yang
Liu, Yani
Zhang, Yu
author_facet Cao, Peng
Guo, Wei
Wang, Jun
Wu, Sanlan
Huang, Yifei
Wang, Yang
Liu, Yani
Zhang, Yu
author_sort Cao, Peng
collection PubMed
description The purposes of this study were to identify physiological and genetic factors that contributed to variability of pemetrexed (PEM) exposure and to optimize the dosing regimens for Chinese non-small cell lung carcinoma patients. A prospective population pharmacokinetics (PPK) research was performed in this population. The PEM concentrations of 192 plasma samples from 116 in-hospital patients were detected. All patients were genotyped for polymorphisms. The PPK model of PEM was developed. The pharmacokinetic behavior of PEM was described by a two-compartment model with first-order elimination. The population typical values were as follows: clearance (CL) 8.29 L/h, intercompartmental clearance (Q) 0.10 L/h, central volume of distribution (V1) 18.94 L and peripheral volume of distribution (V2) 5.12 L. Creatinine clearance (CrCl) was identified as a covariate to CL, and ERCC1 (rs3212986) and CYP3A5 (rs776746) gene polymorphisms as covariates to Q. By using empirical body surface area (BSA)-based dosing strategy, PEM exposure decreased with the elevation of CrCl. Contrarily, CrCl-based dosing strategy exhibited a satisfactory efficacy of achieving the target PEM exposure. BSA-based dosing regimen in current clinic practice is not suitable to achieve the target exposure in PEM chemotherapy of Chinese NSCLC patients. Alternatively, renal function-based dosing strategy is suggested.
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spelling pubmed-94664652022-09-13 Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients Cao, Peng Guo, Wei Wang, Jun Wu, Sanlan Huang, Yifei Wang, Yang Liu, Yani Zhang, Yu Front Pharmacol Pharmacology The purposes of this study were to identify physiological and genetic factors that contributed to variability of pemetrexed (PEM) exposure and to optimize the dosing regimens for Chinese non-small cell lung carcinoma patients. A prospective population pharmacokinetics (PPK) research was performed in this population. The PEM concentrations of 192 plasma samples from 116 in-hospital patients were detected. All patients were genotyped for polymorphisms. The PPK model of PEM was developed. The pharmacokinetic behavior of PEM was described by a two-compartment model with first-order elimination. The population typical values were as follows: clearance (CL) 8.29 L/h, intercompartmental clearance (Q) 0.10 L/h, central volume of distribution (V1) 18.94 L and peripheral volume of distribution (V2) 5.12 L. Creatinine clearance (CrCl) was identified as a covariate to CL, and ERCC1 (rs3212986) and CYP3A5 (rs776746) gene polymorphisms as covariates to Q. By using empirical body surface area (BSA)-based dosing strategy, PEM exposure decreased with the elevation of CrCl. Contrarily, CrCl-based dosing strategy exhibited a satisfactory efficacy of achieving the target PEM exposure. BSA-based dosing regimen in current clinic practice is not suitable to achieve the target exposure in PEM chemotherapy of Chinese NSCLC patients. Alternatively, renal function-based dosing strategy is suggested. Frontiers Media S.A. 2022-08-25 /pmc/articles/PMC9466465/ /pubmed/36105185 http://dx.doi.org/10.3389/fphar.2022.954242 Text en Copyright © 2022 Cao, Guo, Wang, Wu, Huang, Wang, Liu and Zhang. 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
Cao, Peng
Guo, Wei
Wang, Jun
Wu, Sanlan
Huang, Yifei
Wang, Yang
Liu, Yani
Zhang, Yu
Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
title Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
title_full Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
title_fullStr Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
title_full_unstemmed Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
title_short Population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
title_sort population pharmacokinetic study of pemetrexed in chinese primary advanced non-small cell lung carcinoma patients
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9466465/
https://www.ncbi.nlm.nih.gov/pubmed/36105185
http://dx.doi.org/10.3389/fphar.2022.954242
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