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健康志愿者中聚多卡醇连续增加剂量对血小板聚集的影响。

Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers.

作者信息

Arruzazabala M L, Valdés S, Más R, Fernández L, Carbajal D

机构信息

Departamento de Farmacologia, Centro Nacional de Investigaciones Científicas, Havana, Cuba.

出版信息

Pharmacol Res. 1996 Nov-Dec;34(5-6):181-5. doi: 10.1006/phrs.1996.0086.

Abstract

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10 mg day-1) for 7 days. After this period dosage was doubled to 20 mg day-1 for the next 7 days and then again doubled to 40 mg day-1, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.

摘要

聚二十碳五烯醇是一种具有降胆固醇作用的药物,在实验模型、健康志愿者和II型高胆固醇血症患者中均显示出降胆固醇效果。此外,聚二十碳五烯醇在实验模型和健康志愿者中还表现出抗血小板作用。在一项对37名健康志愿者进行的随机、安慰剂对照、双盲研究中,研究了依次增加剂量的聚二十碳五烯醇对血小板聚集的影响。志愿者在安慰剂基线期(每天两片)服用7天,之后在双盲条件下随机接受安慰剂或聚二十碳五烯醇(10毫克/天)7天。在此期间后,剂量在接下来的7天内加倍至20毫克/天,然后再次加倍至40毫克/天,而对照组始终服用安慰剂片。在基线和每个给药步骤后测量血小板聚集以及凝血时间。结果表明,在整个研究过程中聚二十碳五烯醇的抗血小板作用均成功增强,因此提示存在剂量依赖性关系。在第一个给药期未达到显著效果,但在第二个给药期后观察到肾上腺素和ADP诱导的血小板聚集显著降低。最后,在最后一个给药步骤观察到所有激动剂诱导的血小板聚集均受到显著抑制。试验期间凝血时间保持不变。

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