METABOLISM AND PHARMACOKINETICS OF [C-14] DEOXYFRUCTOSYLSEROTONIN CREATININE SULFATE ADMINISTERED ORALLY AND INTRAVENOUSLY TO RATS AND MICE

Deoxyfructosylserotonin (DFS) has been shown in in vitro tests to inhi bit L-DOPA-oxidase and also to suppress the multiplication of Mycobact erium leprae. The possible therapeutic use of DFS makes necessary the study of its metabolic fate in animal models. Labelled [C-14]-DFS was synthesized by condensation of serotonin and [C-14]-glucose and admini stered per os or intravenously to rats and mice. After oral administra tion, some of the radioactivity transited through the intestinal tract to be excreted in feces (20-60% of the dose) and some was destroyed i n the pH conditions of the intestine and further metabolized by the fl ora, producing (CO2)-C-14 in the expired air (10-40% of the dose). Rad ioactivity excreted in the urine amounted to 8-15% after 24 h. After i ntravenous administration, 60-90% of the dose had already been excrete d in the urine after 8 h. Feces and CO2 accounted for 5-10% each. In t he urine, for both routes of administration, beside DFS, half of the r adioactivity corresponded to the glucuronide conjugate, while in the f eces all the radioactivity found was unchanged DFS. Whole animal body autoradiography showed the presence of radioactivity in all the organs (1-2% of the dose) mainly resulting from the incorporation of labelle d carbon from glucose and CO2. These results, obtained in healthy rats , demonstrate poor intestinal absorption of DFS (10% of the dose) and when it is absorbed, rapid urinary excretion. For its possible therape utic use as an anti-leprosy drug in humans, derivatives with higher bi oavailability must be attained.