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从肠道和口腔黏膜吸收的辅酶Q的血浆生物利用度。

The Plasma Bioavailability of Coenzyme Q Absorbed from the Gut and the Oral Mucosa.

作者信息

Vitetta Luis, Leong Andrea, Zhou Joyce, Dal Forno Serena, Hall Sean, Rutolo David

机构信息

The University of Sydney, Sydney Medical School, Faculty of Medicine and Health, Sydney, NSW 2006, Australia.

Medlab Clinical, Sydney, NSW 2015, Australia.

出版信息

J Funct Biomater. 2018 Dec 15;9(4):73. doi: 10.3390/jfb9040073.

Abstract

Coenzyme Q (CoQ) has a central role in the generation of cellular bioenergy and its regulation. The hydrophobicity exhibited by the CoQ molecule leads to reports of poor absorption profiles, therefore, the optimization of formulations and modes of delivery is an ever-evolving therapeutic goal. The aim of this study was to investigate different CoQ formulations. The article summarizes the findings from an Australian comparative study involving adults administered CoQ through different oral delivery platforms. A total of 11 participants (six males and five females) voluntarily participated in a comparative clinical study of three different CoQ formulations across a six-week period, completing 198 person-hours of cumulative contribution equivalent to n = 33 participation. All of the eligible participants (n = 11) administered the three formulations blinded from who the commercial supplier of the formulation was and from what the chemical form of the CoQ was that was being administered. The dosing between the CoQ preparations were dispensed sequentially and were administered following three-week washouts. Three commercial preparations were tested, which included the following: formulations with capsules each containing ubiquinol and ubiquinone (150 mg/capsule), and a liposome ubiquinone formulation (40 mg/mL at 2 actuations of the pump). A significant inter-subject variation in the plasma level of CoQ at baseline that was observed to increase with an increase in age. This trend persisted in the post administration of the different formulations. Furthermore, it was observed that the intestinal absorption and bioavailability of CoQ varied significantly in the plasma between subjects, irrespective of whether the ubiquinol or ubiquinone forms were administered. The administration of CoQ as a liposome for preparation showed the poorest response in bioavailability. Although the ubiquinol capsule form of CoQ was observed to have increased in the plasma versus the ubiquinone capsules and the ubiquinol liposome at the two-hour interval, the inter-subject variation was such that the difference was not significant ( > 0.05). All of the CoQ formulations showed no further increases in their plasma levels over the remaining study period (i.e., four hours). This study further concluded that the intestinal absorption of CoQ is highly variable and is independent of the molecular form administered. Furthermore, it also concludes that liposomes are not an effective vehicle for the oral administration of CoQ, and as such, did not improve the oral mucosal/sublingual absorption and bioavailability of the molecule. Of interest was the observation that with the increasing subject age, there was an observed increase in the baseline plasma CoQ levels in the participants prior to dosing. It was posited that the increase in the baseline plasma levels of CoQ with an increase in age could be due to the loss of skeletal muscle mass, a result that still needs to be verified.

摘要

辅酶Q(CoQ)在细胞生物能量的产生及其调节中起着核心作用。CoQ分子表现出的疏水性导致有关其吸收情况不佳的报道,因此,优化制剂和给药方式是一个不断发展的治疗目标。本研究的目的是调查不同的CoQ制剂。本文总结了一项澳大利亚的比较研究结果,该研究涉及通过不同口服给药平台给予CoQ的成年人。共有11名参与者(6名男性和5名女性)自愿参加了一项为期六周的三种不同CoQ制剂的比较临床研究,累计贡献198人时,相当于n = 33人的参与量。所有符合条件的参与者(n = 11)在不知道制剂的商业供应商以及所给药的CoQ化学形式的情况下服用这三种制剂。CoQ制剂之间的给药是按顺序分发的,并在三周的洗脱期后给药。测试了三种商业制剂,包括:每种胶囊含泛醇和泛醌的制剂(150毫克/胶囊),以及一种脂质体泛醌制剂(泵按压2次时为40毫克/毫升)。观察到基线时CoQ血浆水平存在显著的个体间差异,且该差异随年龄增长而增加。在给予不同制剂后,这种趋势仍然存在。此外,观察到无论给予的是泛醇还是泛醌形式,CoQ在受试者血浆中的肠道吸收和生物利用度在个体间差异很大。以脂质体制剂形式给予CoQ时,生物利用度的反应最差。尽管在两小时时观察到CoQ的泛醇胶囊形式在血浆中的含量相对于泛醌胶囊和泛醇脂质体有所增加,但个体间差异使得这种差异不显著(> 0.05)。在剩余的研究期间(即四小时),所有CoQ制剂的血浆水平均未进一步升高。本研究进一步得出结论,CoQ的肠道吸收高度可变,且与所给药的分子形式无关。此外,研究还得出结论,脂质体不是CoQ口服给药的有效载体,因此,不能提高该分子的口腔黏膜/舌下吸收和生物利用度。有趣的是,观察到随着受试者年龄的增加,给药前参与者的基线血浆CoQ水平有所升高。据推测,CoQ基线血浆水平随年龄增加可能是由于骨骼肌质量的减少,这一结果仍有待验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b53f/6306788/d0a16d692609/jfb-09-00073-g001.jpg

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