Coombes, Z;
Yadav, V;
McCoubrey, LE;
Freire, C;
Basit, AW;
Conlan, RS;
Gonzalez, D;
(2020)
Progestogens are metabolized by the gut microbiota: Implications for colonic drug delivery.
Pharmaceutics
, 12
(8)
, Article 760. 10.3390/pharmaceutics12080760.
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Abstract
Following oral administration, the bioavailability of progestogens is very low and highly variable, in part due to metabolism by cytochrome P450 enzymes found in the mucosa of the small intestine. Conversely, the mucosa in the colon contains much lower levels of cytochrome P450 enzymes, thus, colonic delivery of progestogens may be beneficial. Microbiota in the colon are known to metabolize a great number of drugs, therefore, it is important to understand the stability of these hormones in the presence of colonic flora before developing formulations. The aim of this study was to investigate the stability of three progestogens: progesterone, and its two synthetic analogues, medroxyprogesterone acetate (MPA) and levonorgestrel (LNG), in the presence of human colonic microbiota. Progesterone, MPA, and LNG were incubated in mixed fecal inoculum (simulated human colonic fluid) under anerobic conditions. Progesterone was completely degraded after 2 h, whereas levels of MPA and LNG were still detectable after 24 h. The half-lives of progesterone, MPA, and LNG in fecal inoculum were 28, 644, and 240 min, respectively. This study describes the kinetics of colonic microbial metabolism of these hormones for the first time. MPA and LNG show promise for delivery to the colon, potentially improving pharmacokinetics over current oral delivery methods.
| Type: | Article |
|---|---|
| Title: | Progestogens are metabolized by the gut microbiota: Implications for colonic drug delivery |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/pharmaceutics12080760 |
| Publisher version: | https://doi.org/10.3390/pharmaceutics12080760 |
| Language: | English |
| Additional information: | This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | progesterone; medroxyprogesterone; levonorgestrel; large intestine metabolism; colonic stability; steroids; gastrointestinal bacteria; microbiome |
| 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/10109256 |
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