Singh B N, Williams F M, Whitlock R M, Collett J, Chew C
Clin Pharmacol Ther. 1980 Aug;28(2):159-66. doi: 10.1038/clpt.1980.145.
The beta-blocking potency of timolol was compared with that of propranolol under steady-state conditions in eight healthy subjects. The effects on systolic time intervals in healthy subjects and patients (n = 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 eight times as potent as propranolol. There was wide between-patient variation (2.6 to 13.8) in timolol plasma concentration, and correlation between dose and peak (r = 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 as well as in normal subjects, the data indicated considerable beta-blocking effects for both drugs at the end of a 12-hourly dosing schedule, suggesting that twice-daily timolol and propranolol may be clinically practical.
在8名健康受试者的稳态条件下，比较了噻吗洛尔与普萘洛尔的β受体阻滞效能。针对不同的噻吗洛尔给药方案和血浆浓度，评估了其对健康受试者和冠心病患者（n = 6）收缩期时间间期的影响。通过抑制运动诱发的心动过速来评估β受体阻滞效能。噻吗洛尔的效能是普萘洛尔的8倍。噻吗洛尔血浆浓度在患者之间存在较大差异（2.6至13.8），且剂量与峰值（r = 0.61，p < 0.01）或谷值（r = 0.5，p < 0.01）之间存在相关性。噻吗洛尔血浆浓度与β受体阻滞程度之间的相关性相对较弱（r = 0.45，p < 0.05），与剂量呈线性相关（r = 0.98，p < 0.001）。在健康受试者中，噻吗洛尔和普萘洛尔对收缩期时间间期有不同影响，但在冠心病患者中，等效剂量可延长射血前期、等容收缩时间以及射血前期与左心室射血时间的比值。在患者和正常受试者中，数据表明在每12小时给药一次的方案结束时，两种药物均有显著的β受体阻滞作用，这表明噻吗洛尔和普萘洛尔每日两次给药在临床上可能是可行的。
