Transformation and Excretion of Drugs in Biological Systems. IV. Reabsorption of Biliary Metoclopramide-N<SUP>4</SUP>-glucuronide and -N<SUP>4</SUP>-sulfonate from Rabbit Intestine

Abstract

Of metoclopramide-N4-glucuronide and -N4-sulfonate, both of which were found as the major constituents in the bile after metoclopramide administration to rabbits, reabsorption from the intestine was studied to explore the possibility of the entero-hepatic circulation. Following the administration of the N4-conjugates into the rabbit duodenum, the urinary constituents were quantitatively measured at various times over a period of 12 hours. In the case of the sulfonate, all recovered in the urine was found to be the sulfonate. The result suggests that this conjugate itself may be absorbed from the intestine without being hydrolysed. On the other hand, when the glucuronide was intraduodenally given, at least two features of urinary excretion were observed : One showed that the glucuronide accounts for more than 90% of the total recovered in 8 hours, and the other did that the proportion of it to the total decreases with time. From the examinations for the stability in the aqueous solution and for the urinary excretion after the intravenous administration, it was concluded that the glucuronide may be absorbed from the intestine not only in the parent compound, namely, metoclopramide resulting from the hydrolysis but in the intact form as well as the sulfonate.