Biliary excretion and enterohepatic circulation of two beta‐adrenergic blocking drugs, exaprolol and propranolol in rats

Abstract

Plasma levels and excretion of two beta-adrenoceptor blocking drugs 3H-exaprolol and 3H-propranolol were observed up to 96 h after a single i.v. administration to rats. Terminal half-lives of 26.8 +/- 9.1 h and 51.3 +/- 7.5 h were found for exaprolol and propranolol, respectively. The recovery of 3H radioactivity in feces following i.v. administration of the drugs (34.2 +/- 0.8 per cent and 12.0 +/- 1.3 per cent 3H of exaprolol and propranolol, respectively) is of biliary origin, as 30.7 +/- 3.5 per cent and 13.4 +/- 3.6 per cent 3H of exaprolol and propranolol, respectively, was excreted in the bile after i.v. administration. Enterohepatic circulation of the drugs was studied using the donor-recipient rat method. After intraduodenal administration of donor bile to the recipient rat approximately 50 per cent and 40 per cent of the biliary 3H activity of exaprolol and propranolol, respectively, was re-excreted following absorption. A formula for calculating the amount of the substance together with its metabolites excreted in the bile, urine or feces as a result of enterohepatic circulation has been proposed.