Studies on the Biotransformation of Paeonol by Isotope Tracer Techniques. II. Species Differences in Metabolism

Abstract

Species differences in the metabolism of paeonol (2-hydroxy-4-methoxyacetophenone : I) in mice, rats, guinea pigs and rabbits were studied by the RI tracer technique. After the administration of a single dose of 20 mg (6-70μCi)/kg paeonol [carbonyl-¹⁴C] (I-¹⁴C), radioactive metabolites excreted in the urine were analyzed. The excretion of I-¹⁴C was rapid in all species ; that is, about 83-98% of administered radioactivity was excreted in the urine and feces during two days after the administration. The ¹⁴C-activity excreted in feces was 10.6% in mice, 4.7% in rats, 2.9% in guinea pigs, and 0.8% in rabbits. It is clear that the urine is the major excretion route in all species. 2, 5-Dihydroxy-4-methoxyacetophenone (II), resacetophenone (III) and unchanged I were detected in all species as urinary metabolites. These metabolites were found as the free form, β-glucuronide, sulfate and enzyme-resistant conjugate. The major metabolite in each species was as follows ; mice, II 43.1% ; rats, II 62.0% ; guinea pigs, III 58.1% ; rabbits, III 42.7% and II 42.2%. All the metabolites were conjugated in rats, while the total amount of unconjugated metabolites was 50-60% of total metabolites in other species. Although β-glucuronide and sulfate in rats accounted for 19.9% and 8.2%, respectively, only small amounts of these conjugated forms were excreted in other species. Enzyme-resistant conjugate accounted for 60.2% in rats, but only 35-43% in other species.