Written by Laura McCoubrey
This work studied how the gut microbiome can degrade three orally administered progestogen drugs: progesterone, medroxyprogesterone acetate (MPA), and levonorgestrel (LNG). Progestogens are important drugs used commonly for a range of female indications. However, in their current licensed forms they suffer low and variable blood plasma concentrations. This is partly due to degradation by cytochrome P450 (CYP450) enzymes in the small intestinal wall.
We hypothesised that delivery of these drugs to the colon could be beneficial, as there are lower levels of CYP450 enzymes in the colon compared to the small intestine. Before formulating these drugs for delivery to the colon, we needed to understand how they may fare in the colonic environment. The colon houses the highest density of microbiota in the body, with billions of bacteria per gram content. Gut bacteria are already known to degrade over 170 orally administered drugs, having potentially significant effects on drug efficacy. It was therefore vital that we studied whether the progestogens were susceptible to gut microbiota metabolism.
We found that progesterone was completely degraded in simulated colonic fluid after just 2 hours, whereas MPA and LNG proved much more stable, remaining intact to a certain extent even after 24 hours. Our results highlight MPA and LNG’s promise for colonic delivery.
Feel free to access our full paper freely via this link: https://doi.org/10.3390/pharmaceutics12080760.