Metabolism and excretion in bile of SC4453, a new semi-synthetic derivative of digoxin following an i.v. bolus injection in the guinea-pig.

After a single bolus injection of tritiated SC4453 in the guinea-pig, 36% of the dose was excreted in the bile during the first 6 hours after administration. Solvent partition has shown that 88% of the total radioactivity excreted was soluble in dichloromethane (DCM). Thin layer chromatography analysis of the DCM soluble fraction has shown that SC4453 was mainly excreted unchanged in the bile. Enzymatic hydrolysis of the water soluble fraction has shown that the main partner of conjugation was SC4453 itself. This study has demonstrated a significant enterohepatic circulation for SC4453, suppression of which modified the pharmacokinetic parameters of SC4453 in the guinea-pig. The half-life of elimination decreases from 4.2 hours to 3.22 hours and the volume of distribution (Vdarea) was equal to 2680 ml/kg versus 3692 ml/kg for normal guinea-pig.