l‐bunolol and propranolol: Oral and intravenous β‐adrenoceptor blocking activity in rats compared to dogs and humans

Abstract To determine the pharmacological significance of reported differences between species in l‐bunolol metabolism, oral and intravenous β‐adrenoceptor bloiking activity against an isoproterenol‐induced tachycardia was compared in dogs, rats, and humans. Propranolol was similarly studied in rats and dogs. Species differences in intravenous potency were minimal for both compounds in contrast to oral dose studies. Oral to intravenous ratios of doses causing a comparable degree of β‐adrenoceptor blockade after l‐bunolol were: rat, 212; dog, 4; and human, 5. For propranolol, the oral to intravenous dose ratios were 210 and 32 for the rat and dog, respectively. These pharmacological findings show major differences in the rat compared to dogs and humans and may be explained in part by differences in the urinary excretion patterns of l‐bunolol in the various species.