The biosynthesis of N-(7-hydroxy-2-fluoren-9-C 14-yl)-acetamide from N-2-fluoren-9-C 14-ylacetamide, and its metabolism in the rat and in the guinea pig

Abstract

Carbon-14-labeled N-(7-hydroxy-2-fluorenyl)acetamide was isolated from the urine of guinea pigs given N-2-fluoren-9-C 14-ylacetamide and was purified by column chromatography and carrier crystallization. This compound was administered orally to rats and to guinea pigs. The guinea pigs were sacrificed after 1 day and the rats after 1, 2, and 7 days, respectively. Radioactivity was present in all the rat tissues examined. Isotope seemed to be bound to the soluble (acetate buffer, pH 5) and insoluble rat liver proteins, but was completely absent in guinea pig liver proteins. After 1, 2, and 7 days, rat urine contained 51, 56, and 58%, and the feces 20, 35, and 40%, respectively, of the dose. About 50% of the urinary metabolites were glucuronic acid conjugates, and 14% were sulfuric acid conjugates. These conjugates were mostly those of the compound administered, while some were those of the deacetylated product 7-amino-2-fluorenol, and possibly of polyhydroxylated derivatives. Only small amounts of these compounds were excreted in an unconjugated condition. After 1 day, guinea pig urine and feces accounted for 53% and about 8%, respectively, of the dose. In guinea pig urine, 97% of the radioactivity was in the form of glucuronic acid conjugates, most of which was that of the compound fed.