On the pharmacokinetics of escin

Abstract

Radioactive alpha- and beta-escin were used for pharmacokinetic studies in mice and rats.Labelling was accomplished by tritiating the double bond of tiglic and angelic acids bound to the triterpene ring ester-like.It was seen on whole-body autoradiography that both escin forms are rapidly eliminated from the bile and kidney after iv administration, and that there was a significant, though slight absorption after intragastric or intraduodenal doses.With the exception of the excretory organs, no accumulation was found to occur in the tissues.In agreement with this, radiochemical measurements revealed a rapid fall in the escin concentration in the blood after iv administration.After 6 h the alpha-escin concentration (11 % of the dose) was approximately twice that of beta-escin (6 %).The retarded elimination of alpha-escin was due to a more pronounced plasma-protein binding as determined by ultracentrifugation.Using thick-layer chromatograms it was possible to demonstrate the presence of 2 metabolite fractions in the bile and urine, excretion taking place essentially via the bile.It could be shown both in intact animals and isolated rat liver that metabolic reactions proceed only in 1 portion of the glycoside mixtures referred to as 'escin', and that further the metabolic rate is somewhat faster and involves a larger proportion in the case of alpha-escin.Escins were absorbed more rapidly from the duodenum than from the stomach.As measured by the amounts of escin excreted in the bile and urine, alpha-escin which is water-soluble in the acidic form was absorbed at approximately 11 %, compared with approximately 5 % in the case of beta-escin.After enteric administration the concentration in the blood initially was high, but declined rapidly within 1 h.Based on this finding and on chromatographic analysis of the intestinal lumen following both oral and iv administration, it is concluded tht escins are partly converted to ineffective and nonabsorbing compounds in the intestinal lumen; this probably occurs by the action of microbial enzymes.After enteric administration, portal vein blood was shown to contain only nonmetabolized escin.In toto it is concluded that escins, while constituting readily absorbable compounds, are rapidly eliminated from the liver (either unchanged or metabolized).The chemical nature of the metabolites has not yet been elucidated.