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Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia

This study aimed to evaluate the pharmacokinetics of acipimox in rats under simulated high altitude hypoxia conditions. A sensitive and reliable LC–MS/MS method has been established for the quantitation of acipimox in rat plasma and tissue homogenate and validated according to the guidelines of the...

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Autores principales: Shen, Xin, Li, Gaofu, Wang, Libin, Yu, Huijin, Zhou, Lei, Deng, Huifang, Wang, Ningning, Lai, Chengcai, Zhou, Wei, Gao, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9573116/
https://www.ncbi.nlm.nih.gov/pubmed/36234950
http://dx.doi.org/10.3390/molecules27196413
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author Shen, Xin
Li, Gaofu
Wang, Libin
Yu, Huijin
Zhou, Lei
Deng, Huifang
Wang, Ningning
Lai, Chengcai
Zhou, Wei
Gao, Yue
author_facet Shen, Xin
Li, Gaofu
Wang, Libin
Yu, Huijin
Zhou, Lei
Deng, Huifang
Wang, Ningning
Lai, Chengcai
Zhou, Wei
Gao, Yue
author_sort Shen, Xin
collection PubMed
description This study aimed to evaluate the pharmacokinetics of acipimox in rats under simulated high altitude hypoxia conditions. A sensitive and reliable LC–MS/MS method has been established for the quantitation of acipimox in rat plasma and tissue homogenate and validated according to the guidelines of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Western blotting and enzyme linked immunosorbent assay (ELISA) were used to investigate the expression of lipid metabolism-related proteins and free fatty acid (FFA) levels, respectively. Cell viability was detected using a Cell Counting kit-8 assay (CCK-8). The method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of acipimox between normoxic and hypoxic rats. HCAR2 expression in the hypoxia group was upregulated compared to that in the normoxia group and the levels of FFA decreased more in the hypoxia group. Under the hypoxia condition, the proliferation of HK2 cells was inhibited with increasing concentrations of acipimox. The results provide important and valuable information for the safety and efficacy of acipimox, which indicated that the dosage of acipimox might be adjusted appropriately during clinical medication in hypoxia.
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spelling pubmed-95731162022-10-17 Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia Shen, Xin Li, Gaofu Wang, Libin Yu, Huijin Zhou, Lei Deng, Huifang Wang, Ningning Lai, Chengcai Zhou, Wei Gao, Yue Molecules Article This study aimed to evaluate the pharmacokinetics of acipimox in rats under simulated high altitude hypoxia conditions. A sensitive and reliable LC–MS/MS method has been established for the quantitation of acipimox in rat plasma and tissue homogenate and validated according to the guidelines of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Western blotting and enzyme linked immunosorbent assay (ELISA) were used to investigate the expression of lipid metabolism-related proteins and free fatty acid (FFA) levels, respectively. Cell viability was detected using a Cell Counting kit-8 assay (CCK-8). The method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of acipimox between normoxic and hypoxic rats. HCAR2 expression in the hypoxia group was upregulated compared to that in the normoxia group and the levels of FFA decreased more in the hypoxia group. Under the hypoxia condition, the proliferation of HK2 cells was inhibited with increasing concentrations of acipimox. The results provide important and valuable information for the safety and efficacy of acipimox, which indicated that the dosage of acipimox might be adjusted appropriately during clinical medication in hypoxia. MDPI 2022-09-28 /pmc/articles/PMC9573116/ /pubmed/36234950 http://dx.doi.org/10.3390/molecules27196413 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shen, Xin
Li, Gaofu
Wang, Libin
Yu, Huijin
Zhou, Lei
Deng, Huifang
Wang, Ningning
Lai, Chengcai
Zhou, Wei
Gao, Yue
Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia
title Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia
title_full Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia
title_fullStr Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia
title_full_unstemmed Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia
title_short Quantification of Acipimox in Plasma and Tissues by LC–MS/MS: Application to Pharmacokinetic Comparison between Normoxia and Hypoxia
title_sort quantification of acipimox in plasma and tissues by lc–ms/ms: application to pharmacokinetic comparison between normoxia and hypoxia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9573116/
https://www.ncbi.nlm.nih.gov/pubmed/36234950
http://dx.doi.org/10.3390/molecules27196413
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