The Influence of Atorvastatin, Amlodipine and Ethoxidol on Ubiquinol and Ubiquinone Endogenous Plasma Concentrations in Patients with Chronic Heart Failure.

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current drug metabolism Pub Date : 2023-01-01 DOI:10.2174/1389200224666230913133201

V I Zozina, S N Kondratenko, E V Shikh, L M Krasnykh, E S Melnikov, V G Kukes

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引用次数: 0

Abstract

Background: Coenzyme Q10 is a key component of the mitochondrial respiratory chain and a fat-soluble endogenous antioxidant performing many vital functions in the human body. Many researchers studied the plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and the redox state (ubiquinol/ubiquinone ratio) of CoQ10 in healthy volunteers. However, these parameters in the plasma of patients with chronic heart failure (CHF) remain almost uninvestigated.

Objective: The aim of this case-control study was to investigate the effect of atorvastatin, amlodipine and ethoxidol on endogenous plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with CHF.

Methods: The study included 62 patients with CHF divided into four groups depending on the prescribed therapy. For the quantitative determination of ubiquinol, ubiquinone, and total CoQ10 in the plasma of patients, HPLCMS/ MS was used.

Results: It was established that the endogenous plasma concentration of total CoQ10 in patients with CHF is significantly lower than in healthy volunteers, and the ratio of reduced and oxidized forms of CoQ10 is shifted towards ubiquinone. It was a statistically significant effect of drugs with different physicochemical structures and pharmacological action on the plasma concentrations of ubiquinol, ubiquinone and total CoQ10: atorvastatin administration led to a decrease in the concentration of ubiquinol (-33.3Δ%), and total CoQ10 (-15Δ%), administration of amlodipine contributed to an increase in the levels of ubiquinol (+27.7Δ%) and total CoQ10 (+18.2Δ%), and the administration of ethoxidol caused an increase in the concentration of ubiquinol (+25Δ%), ubiquinone (+17.7Δ%) and total CoQ10 (+20.2Δ%).

Conclusion: Amlodipine is able to neutralize the negative effect of atorvastin on the redox balance of CoQ10 in patients with CHF. An additional prescription of the antioxidant ethoxidol to standard therapy for patients with CHF was substantiated. Determination of the redox state of CoQ10 in plasma can be used to diagnose and assess the degree of oxidative stress in patients with cardiovascular diseases, as well as to assess the efficacy and safety of ongoing pharmacotherapy.

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阿托伐他汀、氨氯地平和乙氧化醇对慢性心力衰竭患者血浆中泛醌和泛酸内源性浓度的影响

背景：辅酶Q10是线粒体呼吸链的重要组成部分，也是一种脂溶性内源性抗氧化剂，在人体内发挥着多种重要功能。许多研究人员研究了健康志愿者血浆中泛醌醇、泛醌酮、总辅酶 Q10 的浓度以及辅酶 Q10 的氧化还原状态（泛醌醇/泛醌酮比率）。然而，慢性心力衰竭（CHF）患者血浆中的这些参数几乎仍未得到研究：本病例对照研究旨在探讨阿托伐他汀、氨氯地平和乙哌噻醇对慢性心力衰竭患者血浆中泛醌、泛酸、总 CoQ10 及其氧化还原状态的影响：研究对象包括 62 名慢性阻塞性肺疾病患者，根据处方疗法的不同分为四组。采用 HPLCMS/ MS 对患者血浆中的泛醌醇、泛醌酮和总辅酶 Q10 进行定量检测：结果表明：CHF 患者血浆中总 CoQ10 的内源性浓度明显低于健康志愿者，还原型和氧化型 CoQ10 的比例向泛醌型倾斜。不同理化结构和药理作用的药物对血浆泛醌醇、泛醌酮和总辅酶Q10浓度的影响具有统计学意义：服用阿托伐他汀会导致泛醌醇浓度下降（-33.3Δ%）和总辅酶Q10的浓度（-15Δ%），服用氨氯地平会导致泛醌醇（+27.7Δ%）和总辅酶Q10的浓度（+18.2Δ%），服用乙氧基醇导致泛醌醇（+25Δ%）、泛醌酮（+17.7Δ%）和总CoQ10（+20.2Δ%）浓度的增加：结论：氨氯地平能够中和阿托伐斯汀对 CHF 患者 CoQ10 氧化还原平衡的负面影响。结论：氨氯地平能中和阿托伐他汀对慢性阻塞性肺疾病患者体内 CoQ10 氧化还原平衡的负面影响。测定血浆中 CoQ10 的氧化还原状态可用于诊断和评估心血管疾病患者的氧化应激程度，以及评估正在进行的药物治疗的有效性和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.