Enhanced glucuronide formation in different tissues following drug administration

A study was made of the o-aminophenol glucuronide synthesis in the slices of the liver, kidney and gastrointestinal tract after the administration of 3,4-benzpyrene, cinchophen, 3-methylcholanthrene, phenobarbital and salicylic acid to elucidate whether the responses of the different tissues are similar to these drugs known to enhance drug metabolism. A 1.6-fold increase of o-aminophenol glucuronide synthesis was found in liver slices 5 days after a single intraperitoneal injection of 3-methylcholanthrene whereas there was no increase in the slices from the kidney or from the various parts of the gastrointestinal tract. The i.p. administration of 3,4-benzpyrene had a similar effect. The intragastric administration of cinchophen for 3 days resulted in a two-fold increase of the synthesis in the slices from the liver, glandular stomach, caecum and colon, and a 3-fold increase was found in the kidney. In the duodenum only a slight increase of activity was observed when the analysis was carried out 24 hr after the last dose, but a 1.6-fold increase was found after 48 hr. The i.p. administration of phenobarbital for 3 days resulted in a 1.4-fold increase of the synthesis in the liver, but no change of activity was found in the kidney or in the various parts of the gastrointestinal tract. The intragastric administration of salicylic acid for 3 days resulted in a 1.9-fold increase in the kidney but only insignificant changes were found in the various parts of the gastrointestinal tract or in the liver when analysed 24 hr after the last dose. The enhancement of the glucuronide biosynthesis caused by the administration of the various drugs thus reveals marked organ specificity.