Colonic bacterial metabolism of corticosteroids
2013
Yadav, Vipul | Gaisford, Simon | Merchant, Hamid A. | Basit, Abdul W.
The aim of this study was to investigate the stability of four corticosteroids in the presence of human colonic bacteria to understand better their luminal behaviour when delivered orally in the treatment of inflammatory bowel disease. The stability of prednisolone, budesonide, beclometasone (17, 21) dipropionate (BDP) and its active metabolite, beclometasone-17-monopropionate (17-BMP), were investigated at three different concentrations following incubation in a mixed faecal inoculum (simulated human colonic fluid) under anaerobic conditions. Prednisolone, at all three concentrations, was completely degraded within 3h. The degradation of budesonide progressed at a slower rate, with complete degradation occurring within 7h; the degradation of the S epimer of budesonide was faster than the R epimer. BDP degraded completely within 2h while its active metabolite 17-BMP was comparatively stable. In contrast to the results in the faecal inoculum, all molecules were stable in the simulated colonic fluid in the absence of human faeces (control). This study demonstrates that prednisolone, BDP and budesonide are completely metabolized in simulated human colonic fluid and confirms the role of colonic bacteria in the metabolism of corticosteroids.
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