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Intestinal Absorption Mechanism of Casearin X

Intestinal Absorption Mechanism of Casearin X in Caco-2 Cells with Modified Carboxylesterase Activity

Caco 2 cells.tif  Intestinal drug absorption.tif

The clerodane diterpene casearin X (1), isolated from the leaves of Casearia sylvestris, is a potential new drug candidate due to its potent in vitro cytotoxic activity at low concentrations. In this work, the intestinal absorption mechanism of 1 was evaluated using Caco-2 cells with and without active carboxylesterases (CES) hydrolysis. The estimation of permeability coefficients was only possible under CES-inhibited conditions, in which 1 is able to cross the Caco-2 cells monolayer. The mechanism is probably by active transport, with no significant efflux, but with a high retention of the compound inside the cells.

Since 1 demonstrates to be a substrate for human carboxyesterases, we can expect that the extent of hydrolysis can significantly lower its bioavailability due to intestinal first-pass metabolism.

This can provide important information to guide chemical modifications and potential alterations in hydrolytic susceptibility of 1.

Kontakt

Prof.
Prof. Dr. Veronika Butterweck Dozentin für Pharmakologie und Pharmakokinetik Telefon : +41 61 228 56 43 E-Mail : veronika.butterweck@fhnw.ch

Institut für Pharma Technology

Hochschule für Life Sciences FHNW Gründenstrasse 40 CH-4132 Muttenz
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