Metabolism of the Glucuronide of N-Hydroxy-2-acetylaminofluorene in the Rat¹ Free

After subcutaneous or intraperitoneal injection of the ¹⁴C-labeled glucuronide of N-hydroxy-2-acetylaminofluorene (N-GlO-AAF-9-¹⁴C), 35–38% of the radioactivity was excreted in the urine and 5–8% in the feces in 6 hr. By 24 hr, almost 70% of the radioactivity had been eliminated (46–49% in the urine and 20% in the feces). Administration of N-GlO-AAF-9-¹⁴C orally led to a slower rate of elimination of radioactivity (9% in the urine and 4% in the feces in 6 hr; 33% in urine and 38% in feces in 24 hr). The total amount of radioactivity excreted in 24 hr (urine + feces) was independent of the mode of administration of the glucuronide. However, the nature of the urinary metabolites of N-GlO-AAF-9-¹⁴C was markedly influenced by the route of administration of the compound, with the least amount of metabolic change taking place after subcutaneous administration.

Following subcutaneous administration of N-GlO-AAF-9-¹⁴C, approximately 60% of the radioactivity injected was excreted in the bile in 24 hr. Almost all (>90%) of the radioactivity in the bilc was accounted for as unaltered N-GlO-AAF-9-¹⁴C. The total amount of radioactivity excreted in 24 hr (bile + urine) in rats with bile duct cannulae was 89% of the dose injected.