Some quantitative evaluation of first-pass metabolism of salicylamide in rabbit and rat.

Abstract

The 1st-pass metabolism of salicylamide (SAM) was studied in rabbits and rats paying main attention to the amounts of the gluconide (SAMG) and sulfate (SAMS) formed. The roles of the intestine and liver for SAMG And SAMS formation during the 1st-pass were examined. An equation was developed to estimate the hepatic 1st-pass metabolism based on the experiments of i.v. and oral administration and intestinal perfusion experiment. Significant species differences were found in these 2 animals. The extent of the 1st-pass metabolism was larger in rabbits (.apprx. 95%) than in rats (.apprx. 60%). Of the 95% 1st-pass metabolism in rabbits, .apprx. 30% is due to the intestine but the remaining 65% is due to the liver. Of the 60% in rats, .apprx. 20 and 40% are estimated to be due to the intestinal and hepatic 1st-pass metabolism, respectively. In rabbits, SAMG and SAMS are formed together in nearly equal amounts in the liver and at the ratio 4:1 in the intestine. In rats, SAMG is exclusively formed in the intestine and SAMS in the liver. The equation described was applied to the data of Gugler who carried out a study on the 1st-pass metabolism of SAM in dogs, and consequently, reported their glucuronidation occurs primarily in the liver but sulfation occurs primarily in the intestine in dogs.