Importance of the urinary excretion in the total elimination of SC4453 in the guinea-pig.

Administration of SC4453 (30 micrograms/kg) in the guinea-pig increases the rate of urinary excretion from 35 ml/kg/24 h to 55 ml/kg/24 h. Ligature of ureters modifies parameters of SC4453 ; t 1/2 beta increases from 4.2 h to 5.6 h and the body clearance diminishes from 622 ml/h/kg (normal guinea-pig) to 530 ml/h/kg in the ligatured ureters guinea-pig. Analysis of the radioactive material excreted in the urine after administration of tritiated SC4453 shows that 58.4% is dichloromethane (DCM) soluble and 41.6% is water soluble. Thin layer chromatography (TLC) of the DCM soluble fraction shows that 74.0% is unchanged SC4453 . After enzymatic hydrolysis of the water soluble fraction, it is shown that 28% is again extractable by DCM of which 57% consists of unchanged SC4453 which is therefore the main partner of conjugated products. Following an i.v. injection of tritiated SC4453 , only 17% of the dose was recovered in urine, against 14% after an intragastric administration. Gastro-intestinal absorption of SC4453 was estimated to be 82.2%.