Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers

The cardiovascular effects of single oral doses of nifedipine (20 mg), atenolol (50 mg), or of their combination were compared with placebo in a double-blind randomized cross-over study in 10 normotensive volunteers. After subjects rested for 2 h, before drug administration, heart rate, blood pressure, stroke volume index, and cardiac index were measured noninvasively. These cardiovascular parameters were then determined prior to and after exercise periods (160 W, 10 min, bicycle ergometry) which were performed 40, 70, 130, 190, 310 min, and 22 h after drug intake. Nifedipine decreased resting diastolic blood pressure (p less than or equal to 0.05) after 2 h, whereas systolic blood pressure remained unchanged and heart rate significantly increased at rest and after exercise. Stroke volume index and cardiac index were unaffected. Atenolol significantly decreased systolic and diastolic blood pressure as well as heart rate; stroke volume index following exercise increased significantly, and cardiac index was unchanged. Administration of the combination caused a significantly more pronounced fall of systolic and diastolic blood pressure as compared with either drug alone, whereas the negative chronotropic effect was not different from that of atenolol. As did atenolol, the combination increased stroke volume index after exercise with no change in cardiac index. Maximum plasma concentrations of nifedipine (37.1 +/- 16.7 ng/ml) and atenolol (276.3 +/- 107.2 ng/ml) and terminal half-life of atenolol (9.9 +/- 2.6 h) were not altered by combined administration of the drugs.