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大鼠中锦葵萼水提取物与卡托普利之间的药代动力学药物相互作用

Pharmacokinetic Herb-Drug Interaction between Calyces Aqueous Extract and Captopril in Rats.

作者信息

Nurfaradilla Shinta Ayu, Saputri Fadlina Chany, Harahap Yahdiana

机构信息

Graduate Program, Faculty of Pharmacy, Universitas Indonesia, Kampus UI, Depok 16424, Indonesia.

Laboratory of Pharmacology, Faculty of Pharmacy, Universitas Indonesia, Kampus UI, Depok 16424, Indonesia.

出版信息

Evid Based Complement Alternat Med. 2020 Jun 17;2020:5013898. doi: 10.1155/2020/5013898. eCollection 2020.

DOI:10.1155/2020/5013898
PMID:32655663
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7317316/
Abstract

L. (Malvaceae) is a traditional medicinal herb widely consumed as a beverage ("hibiscus tea"), and its global popularity is expanding due to health benefits such as blood pressure and cholesterol control. Previous studies showed that is coadministered with antihypertensives and antihyperlipidemics, thus predisposing herb-drug interactions. We investigated the pharmacokinetic interaction between L. aqueous extract and captopril, a frequently prescribed antihypertensive. In this study, chemical profile of L. aqueous extract was identified using HPLC system equipped with a DAD detector at 360 nm and 520 nm. The male Sprague Dawley rats were divided into two groups of six rats. Group I received a single dose of captopril suspension (4.5 mg/200 g body weight (BW) orally (p.o.)) while group II received L. aqueous extract (60 mg/200 g BW; p.o.) daily for two weeks prior to the same captopril dose. Multiple blood samples were collected at predetermined times after captopril administration and the plasma concentration was analyzed using ultrahigh-pressure liquid chromatography-tandem mass spectrometry. Chemical profiling of the L. aqueous extract showed that the extract contains chlorogenic acid, myricetin 3-arabinogalactoside, 5-O-caffeoylshikimic acid, quercetin 3-rutinoside, delphinidin 3-sambubioside, and cyanidin 3-sambubioside. Ingestion of the extract significantly reduced the captopril area under the curve (AUC) (0.1745 (0.1254-0.2429)), AUC0 (0.1734 (0.1232-0.2442))], and peak plasma concentration (0.2119 (0.1337-0.3359)) (geometric mean ratio of the coadministration group to the captopril group (90% CI)). The geometric mean ratios were falling outside the 90% CI of 0.8-1.25 bioequivalent range. Conversely, L. extract increased the apparent total body clearance (Cl/F, 0.0257 ± 0.0115 vs. 0.1418 ± 0.0338 mL/h·kg) and the apparent volume of distribution (Vd/F, 0.0541 ± 0.0226 vs. 0.3205 ± 0.0790 mL/kg). This study indicated that coadministration of L. aqueous extract could change the pharmacokinetic profile of captopril; therefore, its coadministration should be avoided.

摘要

洛神花(锦葵科)是一种传统药草,作为饮品(“洛神花茶”)被广泛饮用,因其具有控制血压和胆固醇等健康益处,在全球范围内越来越受欢迎。先前的研究表明,洛神花与抗高血压药和降血脂药同时服用,因此易发生药草 - 药物相互作用。我们研究了洛神花水提取物与常用抗高血压药卡托普利之间的药代动力学相互作用。在本研究中,使用配备二极管阵列检测器(DAD)的高效液相色谱系统在360nm和520nm波长下鉴定了洛神花水提取物的化学特征。将雄性Sprague Dawley大鼠分为两组,每组六只。第一组口服单剂量卡托普利混悬液(4.5mg/200g体重,经口给药),而第二组在给予相同剂量卡托普利之前,每天经口给予洛神花水提取物(60mg/200g体重),持续两周。在给予卡托普利后的预定时间采集多个血样,并使用超高压液相色谱 - 串联质谱法分析血浆浓度。洛神花水提取物的化学特征分析表明,该提取物含有绿原酸、杨梅素3 - 阿拉伯半乳糖苷、5 - O - 咖啡酰莽草酸、槲皮素3 - 芸香糖苷、飞燕草素3 - 接骨木二糖苷和矢车菊素3 - 接骨木二糖苷。摄入该提取物显著降低了卡托普利的曲线下面积(AUC)[0.1745(0.1254 - 0.2429)]、AUC0[0.1734(0.1232 - 0.2442)]以及血浆峰浓度(0.2119(0.1337 - 0.3359))(联合给药组与卡托普利组的几何平均比值(90%置信区间))。几何平均比值落在生物等效性范围0.8 - 1.25的90%置信区间之外。相反,洛神花提取物增加了表观总体清除率(Cl/F,0.0257±0.0115对0.1418±0.0338mL/h·kg)和表观分布容积(Vd/F,0.0541±0.0226对0.3205±0.0790mL/kg)。本研究表明,同时给予洛神花水提取物可改变卡托普利的药代动力学特征;因此,应避免同时给药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6244/7317316/54a0f0e204f9/ECAM2020-5013898.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6244/7317316/3ec63a65fd92/ECAM2020-5013898.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6244/7317316/9a92093185c9/ECAM2020-5013898.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6244/7317316/54a0f0e204f9/ECAM2020-5013898.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6244/7317316/3ec63a65fd92/ECAM2020-5013898.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6244/7317316/9a92093185c9/ECAM2020-5013898.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6244/7317316/54a0f0e204f9/ECAM2020-5013898.003.jpg

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