Exercise and the pharmacokinetics of propranolol, verapamil and atenolol.

Abstract

The volumes of distribution of the beta-adrenoceptor blocking agents propranolol and atenolol, and the calcium antagonist verapamil, during exercise have been investigated. Changes in the plasma concentrations of atenolol and propranolol during exhaustive exercise at 70% of maximal aerobic power were compared after 1 week of oral treatment (propranolol 80 mg b.d. and atenolol 100 mg once daily) in 12 healthy volunteers. In a second study the effect of 10 min exercise at 50% of maximal aerobic power on steady state plasma concentrations of propranolol, atenolol and verapamil was compared in 7 healthy subjects. The drugs were administered by a continuous intravenous infusion. The plasma concentration of atenolol was not changed by exercise in either study, but the plasma concentrations of propranolol and verapamil were significantly increased in both studies. However, after correction for changes in plasma volume during exercise, the plasma propranolol concentration was not significantly elevated in the second study. From the results it is concluded that exercise led to a reduction in the volume of distribution of propranolol during prolonged exercise (25 min) at 70% Wmax, which was not clearly demonstrable during 10 min exercise at 50% Wmax. The volume of distribution of verapamil was reduced during 10 min exercise at 50% Wmax. No change in the volume of distribution of atenolol during exercise could be shown. The changes in the volumes of distribution of propranolol and verapamil during exercise may contribute to preventing an increase in the half-life of these drugs in patients performing prolonged physical exercise.