eprintid: 10109256
rev_number: 16
eprint_status: archive
userid: 608
dir: disk0/10/10/92/56
datestamp: 2020-09-04 09:45:54
lastmod: 2021-12-10 01:19:05
status_changed: 2020-09-04 09:45:54
type: article
metadata_visibility: show
creators_name: Coombes, Z
creators_name: Yadav, V
creators_name: McCoubrey, LE
creators_name: Freire, C
creators_name: Basit, AW
creators_name: Conlan, RS
creators_name: Gonzalez, D
title: Progestogens are metabolized by the gut microbiota: Implications for colonic drug delivery
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
divisions: G08
keywords: progesterone; medroxyprogesterone; levonorgestrel; large intestine metabolism; colonic stability; steroids; gastrointestinal bacteria; microbiome
note: 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/).
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.
date: 2020-08-12
date_type: published
official_url: https://doi.org/10.3390/pharmaceutics12080760
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1811171
doi: 10.3390/pharmaceutics12080760
lyricists_name: Basit, Abdul
lyricists_id: ABASI56
actors_name: Basit, Abdul
actors_name: Harris, Jean
actors_id: ABASI56
actors_id: JAHAR68
actors_role: owner
actors_role: impersonator
full_text_status: public
publication: Pharmaceutics
volume: 12
number: 8
article_number: 760
citation:        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 <https://doi.org/10.3390/pharmaceutics12080760>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10109256/1/pharmaceutics-12-00760.pdf