In Vitro and In Situ Characterization of the Intestinal Absorption of Capilliposide B and Capilliposide C from Lysimachia capillipes Hemsl.

Xu Zhang,Xiao Cheng,Bo Yang,Yifan Qian,Mancang Gu,Liping Chen,Yali Wu,Di Feng

doi:10.3390/molecules24071227

Abstract

The goal of this investigation was to determine the processes and mechanism of intestinal absorption for capilliposide B (CAPB) and capilliposide C (CAPC) from the Chinese herb, Lysimachia capillipes Hemsl. An analysis of basic parameters, such as drug concentrations, time, and behavior in different intestinal segments was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The susceptibility of CAPB and CAPC to various inhibitors such as P-glycoprotein (P-gp) inhibitor (verapamil); multidrug resistance-associated protein 2 (MRP2) inhibitor (indomethacin); cytochrome P450 protein 3A4 (CYP3A4) inhibitor (ketoconazole); and the co-inhibitor of P-gp, MRP2 and CYP3A4 (cyclosporine A) were assessed using both caco-2 cell monolayer and single-pass intestinal perfusion (SPIP) models. As a result, CAPB and CAPC are both poorly absorbed in the intestines and exhibited segment-dependent permeability. The intestinal permeability of CAPB and CAPC were significantly increased by the co-treatment of verapamil, indomethacin. In addition, the intestinal permeability of CAPB was also enhanced by ketoconazole and cyclosporine A. It can be concluded that the intestinal absorption mechanisms of CAPB and CAPC involve processes such as facilitated passive diffusion, efflux transporters, and enzyme-mediated metabolism. Both CAPB and CAPC are suggested to be substrates of P-gp and MRP2. However, CAPB may interact with the CYP3A4 system.

Highlights

The oral delivery route for the therapeutic administration of drugs remains one of the most desirable and important routes in drug delivery
The concentration of capilliposide B (CAPB) and capilliposide C (CAPC) across caco-2 cell monolayer was detected by liquid chromatography-tandem mass spectrometry (LC-MSn)
The intestinal absorption mechanics and underline and CAPC systematically [31,33,34]. Both compounds showed poor bioavailability and low transport systems of CAPB and CPAC were still unclear. We revealed that both CAPB and exposure in tissues after oral administration [31]

Summary

Introduction

The oral delivery route for the therapeutic administration of drugs remains one of the most desirable and important routes in drug delivery. Many therapeutics are unable to utilize this sought-after delivery route due to the poor solubility and instability of many compounds in gastrointestinal fluids. Properties such as rapid metabolic elimination, low intestinal permeability, and efflux by protein transporters are major obstacles to the oral delivery of various compounds [2]. There have been many attempts to overcome these hurdles described by the aforementioned limitations on oral administration. The efflux transporters, such as the adenosine triphosphate-binding cassette transporters (ABC transporters), play a critical role in the absorption and distribution of drugs in the intestinal

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