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血管紧张素转换酶抑制剂CI-906对原发性高血压患者疗效的初步研究。

Pilot study of the effects of the angiotensin-converting enzyme inhibitor CI-906 on patients with essential hypertension.

作者信息

Gavras I, Vlahakos D, Melby J C, Gavras H

出版信息

J Clin Pharmacol. 1984 Aug-Sep;24(8-9):343-50. doi: 10.1002/j.1552-4604.1984.tb02786.x.

Abstract

The effects of two single doses of the new oral nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor CI-906 on blood pressure and hormone levels are described in eight subjects with essential hypertension. Starting at 0.625 mg, doses were separated by a placebo day and doubled in consecutive patients until the full effect (obtained with 5 and 10 mg) was reached, at which point the remaining patients received the same dosage. All doses, including the smallest, caused ACE suppression to less than 1 per cent of baseline lasting for least 12 hours and remaining below 30 per cent at 48 hours, accompanied by a rise in plasma renin activity (by 10.9 +/- 2.1 ng/ml/hr) and fall in aldosterone (by -12.6 +/- 2.5 ng/100 ml). However, a clinically significant, though partial and short-lived, effect on blood pressure was observed at 2.5 mg. The two highest doses produced similar effects in terms of magnitude of mean blood pressure lowering (by 26 +/- 5 and 25 +/- 2 mm Hg, respectively) and duration (varying from 12 to over 24 hours) regardless of pretreatment renin levels. There was no orthostatic hypotension, tachycardia, or other adverse reaction.

摘要

在8名原发性高血压患者中描述了新型口服非巯基血管紧张素转换酶(ACE)抑制剂CI - 906单次服用两剂对血压和激素水平的影响。起始剂量为0.625毫克,各剂量之间间隔一天服用安慰剂,随后连续患者的剂量翻倍,直至达到最大效果(5毫克和10毫克时获得),此时其余患者接受相同剂量。所有剂量,包括最小剂量,均可使ACE抑制至低于基线水平的1%,持续至少12小时,48小时时仍低于30%,同时伴有血浆肾素活性升高(升高10.9±2.1纳克/毫升/小时)和醛固酮降低(降低-12.6±2.5纳克/100毫升)。然而,在2.5毫克时观察到对血压有临床显著但部分且短暂的影响。无论治疗前肾素水平如何,两种最高剂量在平均血压降低幅度(分别降低26±5和25±2毫米汞柱)和持续时间(从12小时到超过24小时不等)方面产生相似的效果。未出现体位性低血压、心动过速或其他不良反应。

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