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SUMMARYThe therapeutic response to propranolol was evaluated in patients with documented coronary artery disease at doses varying from 40 to 320 mg/day. Therapeutic response was quantified by evaluating exercise performance on a treadmill and then related to plasma propranolol concentration. Plasma propranolol was defined in terms of beta-adrenergic blockade by comparison with dose (concentration) response curves in normal subjects. Individual therapeutic benefit occurred at doses which averaged 144 ± 21 mg/day and at concentrations which averaged 30 ± 7 ng/ml. There was a wide variation between both dose and concentration among the patients at maximum therapeutic response, but when the plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 to 98% of total blockade. Despite the increased exercise performance in these patients, the double product of heart rate and systolic blood pressure was always less, suggesting either an alteration of the relation between myocardial oxygen consumption and the double product during propranolol or a reduction on oxygen delivery to the myocardium as the result of beta-adrenergic blockade of the coronary vasculature. Received April 16, 1975; revision accepted for publication June 20, 1975. 886 utilize plasma propranolol levels have also been con-The present study was designed to re-examine this problem comparing improvement in exercise tolerance with the oral dose of propranolol and its plasma level. We have used a more sensitive and specific method for the measurement of propranolol,10 which appears to be necessary to make meaningful measurement of plasma levels at lower doses of the drug in patients with angina.9 The plasma propranolol concentrations then were interpreted in terms of betaadrenergic receptor blockade by relating them to a dose (concentration) response curve defined in normal subjects. Thus, the plasma levels could be used to assess the extent of beta blockade in the patients' studies. Finally, the hemodynamic responses to increasing propranolol were examined in relation to the therapeutic activity of the drug. MethodsStudies on seven normal subjects (mean age 34 years, range 28-44) were carried out to define the dose (concentration) response relationship during increasing propranolol administration. This relationship was defined in normal subjects because it was not possible to exercise the patients with angina to the level at which adrenergic stimuli were the dominant factor in heart rate control."1 Furthermore, in these patients, propranolol could not be administered to high enough doses to establish a maximum pharmacologic effect, i.e., plateau of heart rate suppression with increased propranolol concentrations. Observations during exercise were made only after initial conditioning using three practice exercise runs. Subjects were studied during a control

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