Comparison of beta-adrenoceptor antagonists as modulators of drug metabolism: effect of lipophilicity on microsomal phase I and II reactions.

The effect of beta-adrenoceptor antagonists with varying lipophilicity on microsomal phase I and II reactions was investigated using rat hepatic microsomes. The degree of inhibition of ethoxyresorufin deethylase paralleled octanol/water partition coefficients: propranolol greater than alprenolol greater than timolol greater than metoprolol greater than atenolol. Propranolol (highly lipophilic) and atenolol (hydrophilic) also had widely different effects on 7-ethoxycoumarin deethylase inhibition and on disopyramide N-dealkylation. However the inhibition of harmol conjugation was not related in the same way to octanol/water partition coefficient as was the phase I reactions.