Ishizaki T, Tawara K
Eur J Clin Pharmacol. 1978 Nov 9;14(1):7-14. doi: 10.1007/BF00560252.
The kinetic disposition and beta-adrenergic blocking action in relation to plasma level of a single oral dose of either timolol or propranolol has been compared in healthy male volunteers. The disposition profiles clearly disclosed different properties of the two drugs, although their half-lives were similar. The available fraction of timolol in the systemic circulation was estimated to be approximately 60% of the dose, and 17.4% was exereted unchanged in urine. The logarithm of plasma concentration showed a significant correlation with the beta-blocking activity assessed by an exercise test. The mean potency ratios of timolol to propranolol as an antagonist of chronotropic effects on exercise tachycardia were 11 to 17 and 3.6 to 5.5 in dose- and concentration-effect relationships, respectively. The absolute reduction of exercise heart rate gave the best coefficient of all measures of beta-blockade. When drug action was measured as beta-blockade assessed by a given response to exercise tachycardia, the effect declined linearly with time, even though plasma levels fell exponentially. This results suggest that the pharmacokinetic t1/2 is much shorter than the pharmacological t1/2.
在健康男性志愿者中比较了单次口服噻吗洛尔或普萘洛尔后，其动力学处置及与血浆水平相关的β-肾上腺素能阻断作用。尽管两种药物的半衰期相似，但处置曲线清楚地显示了它们不同的特性。噻吗洛尔在体循环中的可用分数估计约为剂量的60%，17.4%以原形经尿液排泄。血浆浓度的对数与通过运动试验评估的β-阻断活性呈显著相关。在剂量-效应关系和浓度-效应关系中，噻吗洛尔对普萘洛尔作为运动性心动过速变时性效应拮抗剂的平均效价比分别为11至17和3.6至5.5。运动心率的绝对降低在所有β-阻断测量指标中给出了最佳系数。当通过对运动性心动过速的给定反应评估的β-阻断来测量药物作用时，即使血浆水平呈指数下降，效应也随时间呈线性下降。该结果表明药代动力学t1/2远短于药理t1/2。
