Ueda S, Donnelly R, Panfilov V, Morris A D, Elliott H L
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Br J Clin Pharmacol. 1998 Aug;46(2):127-32. doi: 10.1046/j.1365-2125.1998.00760.x.
To assess the duration and consistency of the pharmacological activity of the dihydropyridine calcium antagonist drug, lacidipine.
Eight healthy normotensive young males participated in a double-blind randomised crossover comparison of single and multiple doses (for 2 weeks) of lacidipine and placebo. The calcium antagonist effects were quantified at 2, 6 and 24 h post dose by the extent of the attenuation of the pressor responses to the intravenous administration of the vasoconstrictors angiotensin II and noradrenaline.
After 2 weeks of treatment, lacidipine consistently and significantly attenuated the pressor responses to both agents at 2 h post dose. At 6 and 24 h post dose there was a significant and progressive decline in the effectiveness of lacidipine in attenuating the pressor responses and for the response to angiotensin II there was no statistically significant effect at either 6 or 24 h post dose.
These results indicate that there is an obvious 'peak' in the pharmacological activity of lacidipine at about 2 h post dose and that this activity is not fully and consistently maintained throughout 24 h.
评估二氢吡啶类钙拮抗剂拉西地平的药理活性持续时间和一致性。
8名健康的血压正常年轻男性参与了拉西地平和安慰剂单剂量及多剂量（持续2周）的双盲随机交叉比较试验。通过静脉注射血管收缩剂血管紧张素II和去甲肾上腺素后升压反应的减弱程度，在给药后2、6和24小时对钙拮抗剂的作用进行量化。
治疗2周后，拉西地平在给药后2小时持续且显著地减弱了对两种药物的升压反应。在给药后6和24小时，拉西地平减弱升压反应的有效性显著且逐渐下降，对于血管紧张素II的反应，在给药后6或24小时均无统计学显著效果。
这些结果表明，拉西地平的药理活性在给药后约2小时有明显的“峰值”，且该活性在24小时内不能完全且持续维持。
