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口服地尔硫䓬对轻度间歇性哮喘患者气道对乙酰甲胆碱及运动反应性的影响。

The effect of oral diltiazem on airway reactivity to methacholine and exercise in subjects with mild intermittent asthma.

作者信息

Harman E, Hill M, Fiebelman R, Pieper J, Hendeles L

机构信息

Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville 32610.

出版信息

Am Rev Respir Dis. 1987 Nov;136(5):1179-82. doi: 10.1164/ajrccm/136.5.1179.

Abstract

The effect of increasing doses of oral diltiazem on airway reactivity to methacholine was evaluated in 10 volunteers with mild asthma. Then the highest tolerated dose was compared with placebo in preventing exercise-induced bronchoconstriction. Methacholine challenges were performed 1 h before and 100 min after placebo or after 30, 60, 90, 120, or 180 mg of oral diltiazem, given in a single-blind, crossover manner on different days within 2 wk. Diltiazem, at doses above 60 mg prolonged the P-R interval of the electrocardiograph but had no significant effect on FVC, FEV1, or FEF25-75. The mean +/- SEM ratio of the dose of methacholine required to produce a 20% decrease in FEV1 (PD20) after diltiazem to the PD20 before diltiazem, i.e., the fold increase in PD20, was not significantly different from placebo at any dose: 0.93 +/- 0.11 after placebo, 1.2 +/- 0.1 after 30 mg, 1.3 +/- 0.3 after 60 mg, 1.2 +/- 0.2 after 90 mg, 1.1 +/- 0.1 after 120 mg, and 1.0 +/- 0.1 after 180 mg. One hundred minutes before a standardized exercise challenge, 120 to 180 mg of oral diltiazem and identically appearing placebo tablets were administered in a randomized, double-blind, crossover design on separate days at least 48 h apart. The mean +/- SEM maximal postexercise decrease in FEV1 was 25.5 +/- 3.3% after placebo and 17.0 +/- 4.8% after diltiazem (p less than 0.01). There was no correlation between change in FEV1 and serum concentrations of diltiazem or its active metabolite desacetyldiltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在10名轻度哮喘志愿者中评估了递增剂量口服地尔硫䓬对气道对乙酰甲胆碱反应性的影响。然后将最高耐受剂量与安慰剂在预防运动诱发性支气管收缩方面进行比较。在2周内不同日期以单盲、交叉方式,在服用安慰剂后1小时以及服用30、60、90、120或180毫克口服地尔硫䓬后100分钟进行乙酰甲胆碱激发试验。地尔硫䓬剂量高于60毫克时可延长心电图的P-R间期,但对用力肺活量(FVC)、第一秒用力呼气容积(FEV1)或25%-75%用力呼气流量(FEF25-75)无显著影响。服用地尔硫䓬后使FEV1降低20%所需的乙酰甲胆碱剂量(PD20)与服用地尔硫䓬前PD20的平均±标准误比值,即PD20的增加倍数,在任何剂量下与安慰剂相比均无显著差异:服用安慰剂后为0.93±0.11,服用30毫克后为1.2±0.1,服用60毫克后为1.3±0.3,服用90毫克后为1.2±0.2,服用120毫克后为1.1±0.1,服用180毫克后为1.0±0.1。在标准化运动激发试验前100分钟,以随机、双盲、交叉设计在至少相隔48小时的不同日期分别给予120至180毫克口服地尔硫䓬和外观相同的安慰剂片。服用安慰剂后FEV1运动后最大平均±标准误下降为25.5±3.3%,服用地尔硫䓬后为17.0±4.8%(p<0.01)。FEV1的变化与地尔硫䓬及其活性代谢物去乙酰地尔硫䓬的血清浓度之间无相关性。(摘要截短至250字)

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