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

Plasma levels and excretion of two beta-adrenoceptor blocking drugs ³H-exaprolol and ³H-propranolol wereobserved 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 drus (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.