Cargando…

Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients

BACKGROUND: Docetaxel is a widely prescribed cytotoxic chemotherapy drug for various cancers and the main dose-limiting toxicity is dose-dependent neutropenia. In China, the current dose regimen for docetaxel frequently results in high inter-individual pharmacokinetic (PK) variability. There is a ve...

Descripción completa

Detalles Bibliográficos
Autores principales: Wei, Jian, Zhang, Yuwen, Li, Ze, Li, Xingang, Zhao, Chenglong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279759/
https://www.ncbi.nlm.nih.gov/pubmed/35845493
http://dx.doi.org/10.21037/atm-22-2619
_version_ 1784746471691649024
author Wei, Jian
Zhang, Yuwen
Li, Ze
Li, Xingang
Zhao, Chenglong
author_facet Wei, Jian
Zhang, Yuwen
Li, Ze
Li, Xingang
Zhao, Chenglong
author_sort Wei, Jian
collection PubMed
description BACKGROUND: Docetaxel is a widely prescribed cytotoxic chemotherapy drug for various cancers and the main dose-limiting toxicity is dose-dependent neutropenia. In China, the current dose regimen for docetaxel frequently results in high inter-individual pharmacokinetic (PK) variability. There is a very urgent need to establish a population PK model of docetaxel for Chinese cancer patients, to predict the area under the curve (AUC) based on the PK model and avoid toxicity, providing optimal drug dose guidance to clinicians. METHODS: Docetaxel was administered at a dose of 75 mg/m(2) once every 3 weeks, and at the scheduled time, blood samples were collected to measure the docetaxel concentration. A nonlinear, mixed-effects modelling approach was used to fit the plasma concentration-time data. A two-compartmental model was selected to characterize the in vivo behavior of docetaxel. Using population modelling, various covariates were explored to ascertain their impact on the docetaxel PK. Monte Carlo simulations were performed to derive the optimal individualized dose regimen. RESULTS: A total of 440 patients with 880 concentration data were collected. The covariate selection indicated that age, body mass index (BMI), and body surface area (BSA) had significant correlations with docetaxel clearance (CL). Bootstrap and visual predictive check (VPC) indicated that a robust and reliable PK model had been established. The final population model was effectively used for simulation to determine docetaxel dose regimens for Chinese cancer patients. Aiming an AUC <2.6 mg/L·h, a simple to use dose regimen was derived based on Monte Carlo simulations. CONCLUSIONS: A population PK model of docetaxel for Chinese cancer patients was developed and validated, showing that age, BMI, and BSA were significantly associated with CL. A simple to use dose regimen table was created to guide clinicians.
format Online
Article
Text
id pubmed-9279759
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher AME Publishing Company
record_format MEDLINE/PubMed
spelling pubmed-92797592022-07-15 Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients Wei, Jian Zhang, Yuwen Li, Ze Li, Xingang Zhao, Chenglong Ann Transl Med Original Article BACKGROUND: Docetaxel is a widely prescribed cytotoxic chemotherapy drug for various cancers and the main dose-limiting toxicity is dose-dependent neutropenia. In China, the current dose regimen for docetaxel frequently results in high inter-individual pharmacokinetic (PK) variability. There is a very urgent need to establish a population PK model of docetaxel for Chinese cancer patients, to predict the area under the curve (AUC) based on the PK model and avoid toxicity, providing optimal drug dose guidance to clinicians. METHODS: Docetaxel was administered at a dose of 75 mg/m(2) once every 3 weeks, and at the scheduled time, blood samples were collected to measure the docetaxel concentration. A nonlinear, mixed-effects modelling approach was used to fit the plasma concentration-time data. A two-compartmental model was selected to characterize the in vivo behavior of docetaxel. Using population modelling, various covariates were explored to ascertain their impact on the docetaxel PK. Monte Carlo simulations were performed to derive the optimal individualized dose regimen. RESULTS: A total of 440 patients with 880 concentration data were collected. The covariate selection indicated that age, body mass index (BMI), and body surface area (BSA) had significant correlations with docetaxel clearance (CL). Bootstrap and visual predictive check (VPC) indicated that a robust and reliable PK model had been established. The final population model was effectively used for simulation to determine docetaxel dose regimens for Chinese cancer patients. Aiming an AUC <2.6 mg/L·h, a simple to use dose regimen was derived based on Monte Carlo simulations. CONCLUSIONS: A population PK model of docetaxel for Chinese cancer patients was developed and validated, showing that age, BMI, and BSA were significantly associated with CL. A simple to use dose regimen table was created to guide clinicians. AME Publishing Company 2022-06 /pmc/articles/PMC9279759/ /pubmed/35845493 http://dx.doi.org/10.21037/atm-22-2619 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Wei, Jian
Zhang, Yuwen
Li, Ze
Li, Xingang
Zhao, Chenglong
Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients
title Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients
title_full Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients
title_fullStr Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients
title_full_unstemmed Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients
title_short Docetaxel population pharmacokinetic modelling and simulation in Chinese cancer patients
title_sort docetaxel population pharmacokinetic modelling and simulation in chinese cancer patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279759/
https://www.ncbi.nlm.nih.gov/pubmed/35845493
http://dx.doi.org/10.21037/atm-22-2619
work_keys_str_mv AT weijian docetaxelpopulationpharmacokineticmodellingandsimulationinchinesecancerpatients
AT zhangyuwen docetaxelpopulationpharmacokineticmodellingandsimulationinchinesecancerpatients
AT lize docetaxelpopulationpharmacokineticmodellingandsimulationinchinesecancerpatients
AT lixingang docetaxelpopulationpharmacokineticmodellingandsimulationinchinesecancerpatients
AT zhaochenglong docetaxelpopulationpharmacokineticmodellingandsimulationinchinesecancerpatients