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急性酒精摄入后 16:0/18:1 和 16:0/18:2 型磷脂酰乙醇胺的合成与消除的差异。

Differences in the Synthesis and Elimination of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 After Acute Doses of Alcohol.

机构信息

Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas.

Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas.

出版信息

Alcohol Clin Exp Res. 2018 May;42(5):851-860. doi: 10.1111/acer.13620. Epub 2018 Mar 30.

Abstract

BACKGROUND

The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers.

METHODS

A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in 15 minutes. Blood and breath samples were collected before, at various times up to 360 minutes postconsumption, and 2, 4, 7, 11, and 14 days after alcohol consumption. Initial rates of PEth synthesis, 360 minutes area under the PEth pharmacokinetic curves (AUCs), and elimination half-lives were determined.

RESULTS

(i) Nonzero PEth levels were observed before alcohol dosing for most participants, despite 7 days of alcohol use monitoring; (ii) 0.4 and 0.8 g/kg doses of alcohol produced proportional increases in PEth levels in all but 1 participant; (iii) the initial rate of synthesis of both PEth homologues did not differ between the 2 doses, but was greater for PEth 16:0/18:2 than PEth 16:0/18:1 at both doses; (iv) the mean AUC of both PEth homologues was higher at 0.8 g/kg than at 0.4 g/kg; (v) the mean AUC of 16:0/18:2 was greater than that of PEth 16:0/18:1 at both alcohol doses; (vi) the mean half-life of PEth 16:0/18:1 was longer than that of PEth 16:0/18:2 (7.8 ± 3.3 [SD] days and 6.4 ± 5.0 [SD] days, respectively); and (vii) there were no sex differences in PEth 16:0/18:1 or 16:0/18:2 pharmacokinetics.

CONCLUSIONS

The results of this study support the use of PEth 16:0/18:1 and 16:0/18:2 as biomarkers for alcohol consumption. Because of consistent pharmacokinetic differences, the levels of these 2 PEth homologues may provide more information regarding the quantity and recentness of alcohol consumption than either alone.

摘要

背景

本研究旨在观察 56 名轻、重度饮酒者饮酒后,16:0/18:1 和 16:0/18:2 型磷脂酰乙醇(PEth)的合成和消除情况。

方法

使用经皮酒精监测仪在实验室饮酒前 7 天和饮酒后 14 天促进酒精戒断。参与者在 15 分钟内摄入 0.4 或 0.8g/kg 的酒精剂量。在饮酒前、饮酒后至 360 分钟的各个时间点以及饮酒后 2、4、7、11 和 14 天采集血样和呼出气样本。确定 PEth 合成的初始速率、360 分钟时的 PEth 药代动力学曲线下面积(AUC)和消除半衰期。

结果

(i)尽管进行了 7 天的酒精使用监测,但大多数参与者在接受酒精给药前仍观察到非零的 PEth 水平;(ii)0.4 和 0.8g/kg 剂量的酒精会使所有参与者除 1 人以外的 PEth 水平呈比例增加;(iii)两种 PEth 同系物的初始合成速率在两种剂量之间没有差异,但在两种剂量下,PEth 16:0/18:2 的合成速率均大于 PEth 16:0/18:1;(iv)两种 PEth 同系物的 AUC 均值在 0.8g/kg 时均高于 0.4g/kg;(v)在两种酒精剂量下,PEth 16:0/18:2 的 AUC 均值均大于 PEth 16:0/18:1;(vi)PEth 16:0/18:1 的平均半衰期长于 PEth 16:0/18:2(分别为 7.8±3.3[SD]天和 6.4±5.0[SD]天);(vii)PEth 16:0/18:1 和 16:0/18:2 的药代动力学无性别差异。

结论

本研究结果支持使用 PEth 16:0/18:1 和 16:0/18:2 作为酒精摄入的生物标志物。由于存在一致的药代动力学差异,这两种 PEth 同系物的水平可能比单独使用时提供更多关于酒精摄入的数量和近期性的信息。

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