Biliary excretion of [14C]succinylsulphathiazole in the rat and rabbit

Abstract

1. After intravenous injection about 30% of the dose (20mg./kg.) of succinylsulphathiazole is excreted unchanged in the bile in 3hr. by the rat, whereas only about 1% is excreted by the rabbit. When the renal pedicles are ligated the biliary excretion of succinylsulphathiazole in the rat increases to about 80% of the dose, but in the rabbit under these conditions the biliary excretion is only 2% of the dose. 2. In the rat, the sulphonamide readily enters the liver and biliary excretion occurs against a concentration gradient from liver to bile; further, the excretory process can be saturated, and can be depressed by the simultaneous administration of phenolphthalein glucuronide or bile salts. 3. In the rabbit, these conditions have not been found; succinylsulphathiazole does not readily enter the liver from the plasma, there is no transfer of the drug from the liver cells to the bile against a concentration gradient, and no saturation or depression of the biliary excretion of succinylsulphathiazole is found. 4. It is suggested that two factors responsible, at least partly, for the low biliary excretion of succinylsulphathiazole in the rabbit are the poor entry of the sulphonamide into the liver in this species and a deficiency of the concentrative mechanism for its excretion in the bile.