Mai, Y;
Gavins, FKH;
Dou, L;
Liu,, J;
Taherali, F;
Alkahtani, ME;
Murdan, S;
... Orlu, M; + view all
(2021)
A non-nutritive feeding intervention alters the expression of efflux transporters in the gastrointestinal tract.
Pharmaceutics
, 13
(11)
, Article 1789. 10.3390/pharmaceutics13111789.
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Abstract
Intestinal interactions with nutrients, xenobiotics and endogenous hormones can influence the expression of clinically relevant membrane transporters. These changes in the gastrointestinal (GI) physiology can in turn affect the absorption of numerous drug substrates. Several studies have examined the effect of food on intestinal transporters in male and female humans and animal models. However, to our knowledge no studies have investigated the influence of a non-nutritive fibre meal on intestinal efflux transporters and key sex and GI hormones. Here, we show that a fibre meal increased the acute expression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug-resistance-associated protein-2 (MRP2) in small intestinal segments in both male and female Wistar rats. Enzyme-linked immunosorbent assays were used for the protein quantification of efflux transporters and hormonal plasma concentration. In male rats, the fibre meal caused the plasma concentration of the GI hormone cholecystokinin (CCK) to increase by 75% and the sex hormone testosterone to decrease by 50%, whereas, in contrast, the housing food meal caused a decrease in CCK by 32% and testosterone saw an increase of 31%. No significant changes in the hormonal concentrations, however, were seen in female rats. A deeper understanding of the modulation of efflux transporters by sex, food intake and time can improve our understanding of inter- and intra-variability in the pharmacokinetics of drug substrates.
| Type: | Article |
|---|---|
| Title: | A non-nutritive feeding intervention alters the expression of efflux transporters in the gastrointestinal tract |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/pharmaceutics13111789 |
| Publisher version: | https://doi.org/10.3390/pharmaceutics13111789 |
| Language: | English |
| Additional information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | food effect; sex differences; hormones; efflux pumps; preclinical drug development; oral delivery; food–drug interactions |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10137466 |
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