Plasma concentration--response relationship of verapamil in the treatment of angina pectoris

Eight patients, mean age 59 years, with stable angina pectoris were investigated with standardized exercise tests to evaluate the plasma concentration--response relationship for verapamil and one of its metabolites, norverapamil. The usual antianginal therapy was discontinued at least 48 h before the start of the investigation. During 4 consecutive days verapamil was administered orally in increasing doses, i.e., no verapamil, 40 mg, 80 mg, or 120 mg t.i.d. Standardized exercise tests were performed each day. In the individual patient the plasma concentration of verapamil increased linearly with the dose given. However, there was a 10- to 30-fold interindividual variation in plasma concentrations of verapamil. The ratio norverapamil/verapamil in plasma decreased with increasing doses of verapamil. The maximal working capacity limited by angina pectoris increased with the plasma concentration of verapamil to a maximum of about 40% for the highest dose. With increasing plasma concentration, the pulse rate decreased both at rest and during exercise. The PQ time increased linearly with the plasma concentration. The systolic and diastolic blood pressure showed a tendency to decrease at the highest plasma levels. Norverapamil seemed not to contribute to the antianginal effect. These results indicate that a correlation exists between the plasma concentration of verapamil and the antianginal effect.