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Biologic Stability of Tauro-23-[⁷⁵Se]Selena-25-Homocholic Acid

Amersham International plc, Amersham, Bucks, United Kingdom
Department of Biochemistry, University of Edinburgh, Edinburgh, United Kingdom

Correspondence: For reprints contact: R. Monks,"Auvergne" Cherry Close, Prestwood, Great Missenden, Buckinghamshire, England HP16 OQD

ABSTRACT

The stability of tauro-23-[⁷⁵Se]selena-25-homocholic acid (SeHCAT) towards deconjugation by the enzyme cholylglycine hydrolase was compared with that of taurocholate: whereas taurocholate underwent 58% deconjugation within 2 hr, SeHCAT suffered only 8% deconjugation plus 5% conversion to an unknown product within 24 hr. Incubation of SeHCAT under anaerobic conditions for 48 hr at 37°C with human fecal organisms resulted in considerable deconjugation, 7-dehydroxylation, and dehydrogenation. Twenty-four hours after the simultaneous administration of SeHCAT and tauro-[24-¹⁴C]cholate to a rabbit the recovery of ⁷⁵Se in bile was 90% of that of ¹⁴C. Forty-eight hours following administration of SeHCAT to a second rabbit residual bile radioactivity revealed 80% deconjugation and dehydroxylation and 60% reconjugation with glycine. Although SeHCAT is more resistant than taurocholate towards modification by fecal bacterial enzymes, within the rabbit it follows the principal metabolic pathways of the natural bile acids.