Extent and Pharmacokinetic Mechanisms of Oral Atenolol-Verapamil Interaction in Man

Chronic coadministration of oral verapamil with oral atenolol resulted in a variable increase in atenolol steady-state plasma concentrations in a group of 10 patients on chronic maintenance therapy. Individual subjects showed changes in area under the plasma atenolol concentration-time curve (AUC) of more than 100%, however group comparisons did not achieve statistical significance unless normalized for verapamil dose. Renal clearance of atenolol was shown to be decreased by more than 25% in 2 subjects studied using intravenous dosing of atenolol. This interaction is likely to contribute to the documented clinical intolerance of combinations of atenolol and verapamil.