Biotransformation studies of prednisone using human intestinal bacteria; Part I: Aerobic incubation

Abstract

Several corticosteroids are commonly used for treatment of conditions associated with inflammatory disorders and as immune modulators. Specifically in cases of ulcerative colitis and the related inflammatory bowel syndromes, these therapeutic agents are administered rectally and are subjected to several intestinal micro floras. The present study aimed to investigate the effect of human intestinal bacterial (HIB) aerobic incubation on prednisone 1 as a model for corticosteroids. Within 96 hours, 1 was mostly transformed by HIB in vitro to various metabolites, which could be separated by column chromatography into two fractions. The first eluted fraction A was found to contain the major metabolite adrenosterone, androst-4-ene-3,11,17-trione m1, whereas fraction B contains metabolite m2, which was identified by chiral HPLC as a mixture of androst-1,4-diene-3,11,17-trione enantiomers. The structures of metabolites m1 and m2 were identified and characterized by spectroscopic techniques, including 2D-NMR and mass spectrometry. Time course of biotransformation of 1 by HIB was also studied.