Duchin K L, Vukovich R A, Dennick L G, Groel J T, Willard D A
Clin Pharmacol Ther. 1980 Jan;27(1):57-63. doi: 10.1038/clpt.1980.9.
Nadolol, a nonselective beta adrenoceptor antagonist, was evaluated in 9 normal sybjects with essential hypertension for ability to inhibit exercise-induced changes in double-product (systolic pressure x heart rate). Propranolol and placebo were included as positive and negative controls. The beta antagonists were administered orally in single doses at 10, 20, 40, and 80 mg on a crossover basis. Both nadolol and propranolol induced comparable dose-related inhibition of double-product. Duration of beta receptor blockade was greater with nadolol than with propranolol; significant inhibition of double-product occurred 24 hr after a single 80-mg dose of nadolol. The antihypertensive effect of nadolol was evaluated in another series of 46 subjects with essential hypertension. The dose of nadolol ranged from 80 to 320 mg once daily. Consistent decreases in supine heart rate (20%) and diastolic blood pressure (9%) from baseline were observed. During steady state, the oral daily dose of nadolol was proportional to the minimum steady-state serum concentration (Cmin) of nadolol (r = 0.75, p less than 0.001) obtained just before the next dose of nadolol. Statistically significant correlation was observed between the antihypertensive effect and the Cmin for nadolol (r = 0.45, p less than 0.05).
纳多洛尔,一种非选择性β肾上腺素能受体拮抗剂,在9名原发性高血压正常受试者中进行了评估,以观察其抑制运动诱发的双乘积(收缩压×心率)变化的能力。普萘洛尔和安慰剂作为阳性和阴性对照。β受体拮抗剂以10、20、40和80毫克的单剂量口服,采用交叉给药方式。纳多洛尔和普萘洛尔均诱导了与剂量相关的双乘积抑制作用。纳多洛尔的β受体阻断持续时间比普萘洛尔长;单次80毫克剂量的纳多洛尔后24小时出现双乘积的显著抑制。在另一组46名原发性高血压受试者中评估了纳多洛尔的降压效果。纳多洛尔的剂量范围为每日一次80至320毫克。观察到仰卧心率(20%)和舒张压(9%)较基线水平持续下降。在稳态期间,纳多洛尔的口服日剂量与在下一次纳多洛尔给药前获得的纳多洛尔最低稳态血清浓度(Cmin)成正比(r = 0.75,p小于0.001)。在纳多洛尔的降压效果与Cmin之间观察到统计学上的显著相关性(r = 0.45,p小于0.05)。