Plasma timolol levels and systolic time intervals

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Abstract
The .beta.-blocking potency of timolol was compared with that of propranolol under steady-state conditions in 8 healthy subjects. The effects on systolic time intervals in healthy subjects and patients (no. = 6) with coronary artery disease were evaluated in relation to varying timolol dose schedules and plasma concentrations. The .beta.-blocking potency was assessed by the inhibition of exercise-induced tachycardia. Timolol was 8 times as potent as propranolol. There was wide between-patient variation (2.6-13.8) in timolol plasma concentration, and correlation between dose and peak (r [correlation coefficient] = 0.61, P < 0.01) or nadir (r = 0.5 P < 0.01). There was a relatively weak correlation between timolol plasma concentration and degree of .beta.-blockade (r = 0.45, P < 0.05) and a linear correlation with dose (r = 0.98 P < 0.001). In healthy subjects timolol and propranolol had variable effects on systolic time intervals, but in patients with coronary artery disease equipotent doses prolonged the preejection period, isovolumetric contraction time and the ratio of the preejection period over the left ventricular ejection time. In patients and in normal subjects, the data indicated considerable .beta.-blocking effects for both drugs at the end of a 12 h dosing schedule, suggesting that twice-daily timolol and propranolol may be clinically practical.