Penbutolol and propranolol: a comparison of their effects on antipyrine clearance in man

The effects of two beta-adrenoceptor antagonists, penbutolol (administered on separate occasions as (+/-)- and (-)-forms) and propranolol, on the kinetics of antipyrine were studied in eight normal subjects. At the same degree of beta-adrenoceptor blockade, as assessed by the lowering of exercise tachycardia, propranolol decreased antipyrine clearance by 31 +/- 11 s.d.% (P less than 0.001) whereas neither of the two penbutolol formulations had a significant effect. The volume of distribution of antipyrine was unchanged following any of the beta-adrenoceptor antagonist treatments. The lack of effect of penbutolol on oxidative drug metabolism is not consistent with in vitro data suggesting a relationship between the lipid solubility of beta-adrenoceptor antagonists and inhibition of metabolism.