Studies on Metabolism and Disposition of Sizofiran (SPG), an Anti-tumor Polysaccharide. II. Effects on Hepatic Drug-Metabolizing Enzyme System in Rats

Abstract

The effect of a single or multiple administration of sizofiran (SPG), an anti-tumor polysaccharide, on a hepatic drug-metabolizing enzyme system was studied in rats. When SPG was given intravenously at a single dose of 0.5 or 10 mg/kg, no alteration was observed in activities of aminopyrine (AP) N-demethylase and aniline hydroxylase, and in cytochrome P-450 (P-450) content in the livers of rats 48 h after dosing. However, only AP demethylase activity decreased by 34% after the administration of 200 mg/kg. Similarly, no change in the hepatic enzyme activities and P-450 content was observed for up to 180 d after a single dose of 10 mg/kg. Subcutaneous treatment of animals with either 10 or 40 mg/kg dose for 3 and 6 months resulted in no alteration in the enzyme activities and P-450 content. These results may indicate that the therapeutically effective dose of SPG has no effect on a hepatic drug-metabolizing enzyme system in rats.