The complex metabolism of poststerone in male rats

• Poststerone (Post) has far greater bioavailability than 20-hydroxyecdysone. • Post is involved in an entero-hepatic cycle and is metabolised by organs and microbiome. • Several Post metabolites have been isolated and identified from rat bile. • Post and its metabolites are predominantly excreted in the faeces. • In line with their bioavailability, Post and its metabolites are also present in the urine. Ecdysteroids are not endogenous to mammals, but are normal components of the food intake of many mammalian species consuming phytoecdysteroid-containing plants. The most frequently encountered phytoecdysteroid is 20-hydroxyecdysone (20E). Several pharmaceutical effects have been observed after ecdysteroid injection or ingestion, but it is not clear to what extent metabolites generated in the mammalian body contribute to these effects. The C21-ecdysteroid poststerone (Post) is a metabolite of 20E in rodents. Post analogues are key intermediates in the metabolism of exogenous ecdysteroids possessing a C20/22-diol. The pharmacokinetics, bioavailability and metabolism of Post have been assessed in male rats after ingestion and injection. The bioavailability of Post is significantly greater than that of 20E and the presence of an efficient entero-hepatic cycle allows Post to be effectively metabolised to a wide range of metabolites which are excreted mainly in the faeces, but also to some extent in the urine. Several of the major metabolites in the bile have been identified unambiguously as 3- epi -poststerone, 16α-hydroxypoststerone, 21-hydroxypoststerone and 3- epi -21-hydroxypoststerone. Conjugates are also present. Parallels are drawn to the metabolism of endogenous vertebrate steroid hormones, to which Post bears more similarity than 20E.