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The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma

Mitotane is the only drug approved to treat adrenocortical carcinoma (ACC), and a relationship of pharmacokinetic/pharmacodynamic has been characterized. However, limited evidence concerning affecting factors in large interindividual variability of the pharmacokinetics of mitotane is available. To a...

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Autores principales: Liu, Xin, Shang, Junmei, Fu, Qiang, Lu, Lin, Deng, Jianhua, Tang, Yan, Li, Jiantao, Mei, Dan, Zhang, Bo, Zhang, Shuyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281498/
https://www.ncbi.nlm.nih.gov/pubmed/35847963
http://dx.doi.org/10.3389/fonc.2022.919027
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author Liu, Xin
Shang, Junmei
Fu, Qiang
Lu, Lin
Deng, Jianhua
Tang, Yan
Li, Jiantao
Mei, Dan
Zhang, Bo
Zhang, Shuyang
author_facet Liu, Xin
Shang, Junmei
Fu, Qiang
Lu, Lin
Deng, Jianhua
Tang, Yan
Li, Jiantao
Mei, Dan
Zhang, Bo
Zhang, Shuyang
author_sort Liu, Xin
collection PubMed
description Mitotane is the only drug approved to treat adrenocortical carcinoma (ACC), and a relationship of pharmacokinetic/pharmacodynamic has been characterized. However, limited evidence concerning affecting factors in large interindividual variability of the pharmacokinetics of mitotane is available. To address this question, a retrospective analysis was performed on ACC Chinese patients treated with mitotane for more than 3 months. Mitotane plasma trough concentrations were detected at the steady state, and CYP2B6, CYP3A4, and pregnane X receptor (PXR) polymorphisms were genotyped. After examining homogeneous pharmacologic data, we restricted the analyses to 36 patients that received mitotane for a median (interquartile range, IQR) of 9 months (5.00–22.50) with a median dose of 2 g/day (2.00–2.50). As a result, drug exposure was significantly influenced by the cumulative dose of mitotane, and CYP2B6 516GG and CYP2B6 26570CC were at high risk to be below the therapeutic range of mitotane. No association was found between mitotane concentrations with CYP3A4 or PXR polymorphism. Our data firstly indicated that the cumulative dose of mitotane and polymorphisms of CYP2B6 516 and CYP2B6 26570 might significantly affect mitotane plasma trough concentrations in Chinese ACC patients.
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spelling pubmed-92814982022-07-15 The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma Liu, Xin Shang, Junmei Fu, Qiang Lu, Lin Deng, Jianhua Tang, Yan Li, Jiantao Mei, Dan Zhang, Bo Zhang, Shuyang Front Oncol Oncology Mitotane is the only drug approved to treat adrenocortical carcinoma (ACC), and a relationship of pharmacokinetic/pharmacodynamic has been characterized. However, limited evidence concerning affecting factors in large interindividual variability of the pharmacokinetics of mitotane is available. To address this question, a retrospective analysis was performed on ACC Chinese patients treated with mitotane for more than 3 months. Mitotane plasma trough concentrations were detected at the steady state, and CYP2B6, CYP3A4, and pregnane X receptor (PXR) polymorphisms were genotyped. After examining homogeneous pharmacologic data, we restricted the analyses to 36 patients that received mitotane for a median (interquartile range, IQR) of 9 months (5.00–22.50) with a median dose of 2 g/day (2.00–2.50). As a result, drug exposure was significantly influenced by the cumulative dose of mitotane, and CYP2B6 516GG and CYP2B6 26570CC were at high risk to be below the therapeutic range of mitotane. No association was found between mitotane concentrations with CYP3A4 or PXR polymorphism. Our data firstly indicated that the cumulative dose of mitotane and polymorphisms of CYP2B6 516 and CYP2B6 26570 might significantly affect mitotane plasma trough concentrations in Chinese ACC patients. Frontiers Media S.A. 2022-06-30 /pmc/articles/PMC9281498/ /pubmed/35847963 http://dx.doi.org/10.3389/fonc.2022.919027 Text en Copyright © 2022 Liu, Shang, Fu, Lu, Deng, Tang, Li, Mei, Zhang 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 Oncology
Liu, Xin
Shang, Junmei
Fu, Qiang
Lu, Lin
Deng, Jianhua
Tang, Yan
Li, Jiantao
Mei, Dan
Zhang, Bo
Zhang, Shuyang
The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma
title The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma
title_full The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma
title_fullStr The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma
title_full_unstemmed The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma
title_short The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma
title_sort effects of cumulative dose and polymorphisms in cyp2b6 on the mitotane plasma trough concentrations in chinese patients with advanced adrenocortical carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281498/
https://www.ncbi.nlm.nih.gov/pubmed/35847963
http://dx.doi.org/10.3389/fonc.2022.919027
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