Biologic stability of tauro-23-[75Se] selena-25-homocholic acid.
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 degrees C with human fecal organisms resulted in considerable deconjugation, 7 alpha-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.
Monks
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Amersham International plc, Bucks, United Kingdom.
Boyd
G S
GS
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001421:Bacteria, Anaerobic / Q000201:enzymology; D002250:Carbon Radioisotopes / Q000378:metabolism; D004355:Drug Stability; D005243:Feces / Q000382:microbiology; D006801:Humans; D006868:Hydrolysis; D011817:Rabbits; D012644:Selenium Radioisotopes / Q000378:metabolism*; D013656:Taurocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D013997:Time Factors
D002250:Carbon Radioisotopes; D012644:Selenium Radioisotopes; D013656:Taurocholic Acid; C033638:23-seleno-25-homotaurocholic acid; D000581:Amidohydrolases; C023154:choloylglycine hydrolase