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[健康受试者中氯噻嗪的剂量-反应关系]

[Dose-response relationship of xipamide in healthy subjects].

作者信息

Knauf H, Haase W, Mutschler E

出版信息

Arzneimittelforschung. 1980;30(9):1599-607.

PMID:7006620
Abstract

To establish a dose-effect relationship for the xipamide diuretic in double-blind trials 0, 5, 10, 20 and 40 mg of xipamide were administered to 5 groups of 6 to 14 healthy test persons in each group. Before, during and after the 15-d period of application all the blood electrolytes as well as the metabolism parameters of glucose, uric acid, cholesterol, neutral fats as well as creatinine and urea were determined. Similarly during the entire period of investigation the 24-h urine samples were collected daily and from these the electrolyte excretion as well as the endogenic creatinine clearance were determined. It was found that diuresis and natriuresis significantly enhanced in comparison with placebo were already achieved with 5 mg xipamide per day, they could no further be increased by higher doses. Much rather at 40 mg xipamide per day a significant hypokalaemia as well as a light hypercalcaemia developed. Independently of the dose, during the period of investigation a light, fully compensated hypochloraemic alkalosis developed. Regarding the metabolic processes a slight increase in the uric acid and cholesterol blood levels was observed, while the blood-sugar level, the triglycerides as well as the endogenic creatinine clearance remained unaffected. It can be concluded from the investigations that maximum natriuresis and diuresis can already be achieved with a daily xipamide dose of 5 mg, while side effects can be kept at a minimum.

摘要

为在双盲试验中确定西帕胺利尿剂的剂量效应关系,将0、5、10、20和40毫克西帕胺分别给予5组健康受试人员,每组6至14人。在应用药物的15天期间之前、期间和之后,测定了所有血液电解质以及葡萄糖、尿酸、胆固醇、中性脂肪以及肌酐和尿素的代谢参数。同样,在整个研究期间,每天收集24小时尿液样本,并测定其中的电解质排泄以及内生肌酐清除率。结果发现,与安慰剂相比,每日5毫克西帕胺即可显著增强利尿和利钠作用,更高剂量无法进一步增加利尿和利钠效果。相反,每日40毫克西帕胺会导致明显的低钾血症以及轻度高钙血症。与剂量无关,在研究期间出现了轻度的、完全代偿性的低氯性碱中毒。关于代谢过程,观察到尿酸和胆固醇血水平略有升高,而血糖水平、甘油三酯以及内生肌酐清除率未受影响。从研究中可以得出结论,每日5毫克西帕胺剂量即可实现最大利钠和利尿效果,同时可将副作用降至最低。

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