Abstract

¹⁴C-Propranolol was Completerly absorbed after p.o. dosing to rats and dogs and at least 70% in monkeys. The plasma half-life was approximately 45 minutes in dog after both i.v. and P.O. administration but was of the order of 6 hours in a monkey dosed p.o. at 4.4 mg/kg, peak blood levels of propranolol and 4-hydroxypropranolol being observed at approximately 1 hour after p.o. dosing. Excretion of radioactivity was almost completely via the urine in monkey but rats and dogs excreted approximately 25% via the feces. The fecal excretion was shown to be the result of biliary excretion in rat and dog. Biliary excretion was also shown in monkey, but presumably there must be enterohepatic circulation in this species. Extensive metabolism was shown to occur and the presence of the active 4-hydroxy-propranolol in blood after p.o. dosing was shown. Naphthoxylactic acid was shown to be an important metabolite in the three species. A slightly basic major metabolite was observed in both blood and urine of all the species studied. Propranolol was concentrated in the lung and, to a lesser extent, in brain, liver, kidney and heart; after p.o. dosing each of these tissues probably contained approximately 25% of the apparent propranolol as the 4-hydroxy derivative. Similar concentration of the major metabolite in tissues was not observed.