First-pass effect and intrinsic clearance of propranolol and pindolol in the isolated perfused rat liver.

This study investigated the first-pass effect (E) and total hepatic intrinsic clearance (Clint) of propranolol and pindolol by means of an isolated rat liver perfusion model. It was shown that propranolol has a highly significantly greater E and Clint than pindolol. These marked differences between the drugs may be accounted for by the strong initial binding of propranolol to liver sites, a phenomenon possibly related to the greater lipid solubility of propranolol compared with pindolol.