Progestogens are metabolized by the gut microbiota: Implications for colonic drug delivery

Zoe Coombes, Vipul Yadav, Laura E. McCoubrey, Cristina Freire, Abdul W. Basit, R. Steven Conlan, Deyarina Gonzalez

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Article number760
Pages (from-to)1-10
Number of pages10
JournalPharmaceutics
Volume12
Issue number8
DOIs
StatePublished - Aug 2020

Keywords

  • Colonic stability
  • Gastrointestinal bacteria
  • Large intestine metabolism
  • Levonorgestrel
  • Medroxyprogesterone
  • Microbiome
  • Progesterone
  • Steroids

ASJC Scopus subject areas

  • Pharmaceutical Science

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