Interindividual pharmacokinetic and pharmacodynamic variability of different beta blockers

Abstract

Hepatic drug metabolism influenced by genetic and environmental factors is a major source of variation in the response to a number of beta-adrenoceptor antagonists. The first study described here was carried out to define the role of a genetic determinant (debrisoquine-type oxidation polymorphism) on plasma concentration of bopindolol and its pharmacological effect. Atenolol was used as a negative and metoprolol as a positive control. In a second study, the relative potency and duration of action of bopindolol were assessed in comparison to atenolol and slow-release oxprenolol. The first study was carried out using 10 healthy volunteers (6 extensive and 4 poor metabolizers), and the second study was carried out using 12 volunteers, all of whom were extensive metabolizers. Genetic polymorphism did not influence the kinetic behavior or pharmacological effects of atenolol. The elimination of bopindolol was slightly but significantly prolonged in poor metabolizers, but this did not significantly alter the cardiac effects of the drug. In the case of metoprolol poor metabolizers showed a significant prolongation of drug elimination, and this was associated with a significant prolongation of the cardiac effects of the drug. The second study revealed that, in terms of cardiac beta-adrenoceptor blockade, 1 mg bopindolol was equipotent to 100 mg atenolol or 160 mg slow-release oxprenolol and that both bopindolol and atenolol had a longer duration of action than slow-release oxprenolol. It is concluded that bopindolol is a potent beta-adrenoceptor antagonist with a very long duration of action which shows little interindividual variability.