姜黄素在肠道吸收屏障的潜在 P-糖蛋白介导的草药-药物相互作用。

Potential P-glycoprotein-mediated herb-drug interaction of phyllanthin at the intestinal absorptive barrier.

机构信息

Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

出版信息

J Pharm Pharmacol. 2019 Feb;71(2):213-219. doi: 10.1111/jphp.13019. Epub 2018 Sep 25.

DOI:10.1111/jphp.13019

PMID:30251430

Abstract

OBJECTIVES

This study investigated the absorptive potential of phyllanthin across the polarized Caco-2 monolayers and the potential role of phyllanthin in P-glycoprotein (P-gp)-mediated drug interaction.

METHODS

The absorptive potential of phyllanthin was predicted from its apparent permeability (P ) across the Caco-2 monolayers under the pH gradient condition (pH 6.5 -7.4 ) at 37°C. Integrity of paracellular transport was assessed by monitoring transepithelial electrical resistance (TEER) and lucifer yellow (LY) leakage. P-gp-mediated interaction was evaluated by transport studies of phyllanthin and rhodamine-123.

KEY FINDINGS

The absorptive P of phyllanthin (34.90 ± 1.18 × 10 cm/s) was in the same rank order as the high permeable theophylline and antipyrine. Phyllanthin transport in the absorptive and secretive directions was comparable (the efflux ratio (ER) of 1.19 ± 0.01). Phyllanthin caused no changes in TEER nor LY leakage in the monolayers. However, phyllanthin increased rhodamine-123 ER in a concentration-dependent manner, suggesting its inhibition on P-gp function. In addition, phyllanthin aqueous solubility was <5 μg/ml at 37°C.

CONCLUSIONS

Phyllanthin is a highly permeable compound that could passively diffuse through the absorptive barrier via transcellular pathway with little hindrance from P-gp. Phyllanthin could interfere with transport of P-gp drug substrates, when concomitantly administered. In addition, aqueous solubility could be a limiting factor in phyllanthin absorption.

摘要

目的

本研究旨在考察叶下珠素在 Caco-2 单层细胞中的吸收潜力及其在 P 糖蛋白（P-gp）介导的药物相互作用中的潜在作用。

方法

在 37°C 下，通过测定叶下珠素在 pH 梯度条件下（pH 6.5-7.4）穿过 Caco-2 单层细胞的表观渗透系数（P ）来预测其吸收潜力。通过监测跨上皮电阻（TEER）和荧光素黄（LY）渗漏来评估细胞旁转运的完整性。通过叶下珠素和罗丹明 123 的转运研究来评估 P-gp 介导的相互作用。

主要发现

叶下珠素的吸收性 P（34.90±1.18×10-6cm/s）与高渗透性茶碱和安替比林相当。叶下珠素在吸收和分泌方向的转运相当（外排比（ER）为 1.19±0.01）。叶下珠素对单层细胞的 TEER 或 LY 渗漏没有影响。然而，叶下珠素以浓度依赖的方式增加了罗丹明 123 的 ER，表明其抑制了 P-gp 的功能。此外，叶下珠素在 37°C 时的水溶解度<5μg/ml。