Prefeeding-dependent anaerobic metabolization of xenobiotics by intestinal bacteria--methods for acarbose metabolites in an artificial colon.

The biotransformation of Acarbose (Bay g 5421) by an artificial in vitro system with viable intestinal microorganisms was investigated. The bacteria were obtained from the colon of man or from the caecum and colon of rats and were incubated anaerobically with 14C-Acarbose in a nutrient solution. The metabolites were separated and purified by chromatographic methods and identified by nuclear magnetic resonance (1H; 13C) spectrometry and by mass spectrometry. Metabolites in man and rat are component 2 (minus the terminal glucose of Acarbose), a basic disaccharide consisting of rings B and C, and component 1. This latter substance is formed, after hydrolytic cleavage of the internal glucose of Acarbose, by spontaneous rearrangement of rings A and B (Acarviosine) into a tricyclic oxazolidine. The metabolite pattern of Acarbose is changed profoundly after several weeks of pretreatment of man or rat with this compound. The microflora adapted in such a manner yields in addition methylated, hexosylated, and n-butyroylated derivatives of Acarbose and/or component 2.