@article {Du Souich279, author = {P Du Souich and H Maurice and L H{\'e}roux}, title = {Contribution of the small intestine to the first-pass uptake and systemic clearance of propranolol in rabbits.}, volume = {23}, number = {2}, pages = {279--284}, year = {1995}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Epithelial cells of the intestine enclose isozymes able to metabolize propranolol, raising the possibility that the gut contributes with the liver to the first-pass uptake and systemic clearance of propranolol. To assess the role of the liver in the first-pass uptake, propranolol was injected into the jugular vein and a mesenteric vein of anesthetized New Zealand rabbits, and blood samples were drawn from the abdominal aorta, or it was injected into the intestine and samples were drawn simultaneously from the portal vein and the abdominal aorta. Extraction of propranolol by the liver was estimated to be 96-97\%. To assess the intestinal extraction of oral propranolol, a porto-cava transposition was conducted in two groups of animals, and propranolol was injected into the first 30 cm of the small intestine or into the jugular vein and samples were withdrawn from the abdominal aorta; propranolol extraction by the intestine was 43\%. To document the contribution of the intestine in the systemic clearance of propranolol, propranolol was injected into the jugular vein and blood samples were drawn simultaneously from the abdominal aorta (before the gut) and from the portal vein (after the gut); propranolol extraction from the systemic circulation by the intestine was 24\%. Only the liver generated detectable amounts of conjugated metabolites of propranolol. In the in vitro studies, it was shown that propranolol was rapidly metabolized by the liver, yielding 4-hydroxypropranolol and conjugates of propranolol; propranolol metabolism in the proximal small intestine was slower and yielded only 4-hydroxypropranolol.(ABSTRACT TRUNCATED AT 250 WORDS)}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/23/2/279}, eprint = {https://dmd.aspetjournals.org/content/23/2/279.full.pdf}, journal = {Drug Metabolism and Disposition} }