Effect of diltiazem on the reduction in exercise-induced tachycardia and kinetic parameters of propranolol or atenolol.

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The pharmacokinetic and pharmacodynamic interactions between diltiazem and propranolol, or atenolol were investigated in healthy volunteers. Diltiazem (30mg) or placebo was given three times daily for 3 days, and 30 min before administration of a β-adrenoceptor blocking drug given on the 4th day. A single dose of propranolol (20mg), or atenolol (50mg) was administered in a randomized, double-blind, crossover fashion. Exercise tests on a cycle ergometer were carried out before and after β-adrenoceptor blocking drug. Diltiazem significantly increased the AUC and elimination half-life of propranolol. The cardiac β-adrenoceptor blocking effect, as indicated by the percentage reduction in heart rate during exercise, tended to increase following diltiazem pretreatment, in comparison with placebo. In contrast, diltiazem did not significantly affect atenolol pharmacokinetics and pharmacodynamics. These results indicated that diltiazem impaired the total clearance of propranolol, which is principally metabolized by oxidative pathway in the liver. This kinetic interaction between diltiazem and propranolol may be partly related to the reduction in exercise-induced tachycardia.
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