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静脉注射 3,4-二羟苯乙酸和 3-羟苯乙酸在大鼠体内的单剂量药代动力学。

Single dose pharmacokinetics of intravenous 3,4-dihydroxyphenylacetic acid and 3-hydroxyphenylacetic acid in rats.

机构信息

Pharmaceutical Biology, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Department of Pharmaceutics, College of Pharmacy, University of Florida, 1345 Center Drive, Gainesville, FL 32610, USA.

出版信息

Fitoterapia. 2020 Apr;142:104526. doi: 10.1016/j.fitote.2020.104526. Epub 2020 Feb 22.

Abstract

3,4-Dihydroxyphenylacetic acid (DOPAC) and 3-hydroxyphenylacetic acid (3-HPAA) are intestinal metabolites of the dietary flavonoid quercetin. DOPAC reportedly showed anxiolytic activity after i.p. administration in rats. The fate of these metabolites after consumption, and the pharmacological properties of 3-HPAA in the body are largely unknown. The aim of the current study was to characterize pharmacokinetic properties of DOPAC and 3-HPAA after intravenous bolus application in rats. UHPLC-MS/MS methods for quantification of DOPAC and 3-HPAA levels in lithium heparin Sprague Dawley rat plasma were developed and validated according to international regulatory guidelines. Non-compartmental and compartmental analyses were performed. Pharmacokinetic profiles of DOPAC and 3-HPAA followed a two-compartment body model, with a fast distribution into peripheral tissues (half-lives of 3.27-5.26 min) and rapid elimination from the body (half-lives of 18.4-33.3 min).

摘要

3,4-二羟基苯乙酸(DOPAC)和 3-羟基苯乙酸(3-HPAA)是膳食类黄酮槲皮素的肠道代谢物。据报道,DOPAC 经腹腔注射给药后具有抗焦虑活性。这些代谢物在消耗后的命运,以及 3-HPAA 在体内的药理特性在很大程度上是未知的。本研究的目的是描述静脉推注后 DOPAC 和 3-HPAA 在大鼠体内的药代动力学特征。根据国际监管指南,建立和验证了用于锂肝素 Sprague Dawley 大鼠血浆中 DOPAC 和 3-HPAA 水平定量的 UHPLC-MS/MS 方法。进行了非房室和房室分析。DOPAC 和 3-HPAA 的药代动力学特征符合双室体模型,快速分布到外周组织(半衰期为 3.27-5.26 分钟),并迅速从体内消除(半衰期为 18.4-33.3 分钟)。

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