THE EFFECT OF ORAL DILTIAZEM ON AIRWAY REACTIVITY TO METHACHOLINE AND EXERCISE IN SUBJECTS WITH MILD INTERMITTENT ASTHMA
THE EFFECT OF ORAL DILTIAZEM ON AIRWAY REACTIVITY TO METHACHOLINE AND EXERCISE IN SUBJECTS WITH MILD INTERMITTENT ASTHMA
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DOI：
10.1164/ajrccm/136.5.1179
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发表时间：
1987-11-01
期刊：
影响因子：
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通讯作者：
HENDELES, L
中科院分区：
文献类型：
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作者：
HARMAN, E;HILL, M;HENDELES, L
在10名轻度哮喘志愿者中评价了增加口服地尔硫卓剂量对乙酰甲胆碱气道反应性的影响。然后将最高耐受剂量与安慰剂在预防运动诱导的支气管收缩方面进行比较。乙酰甲胆碱激发试验在安慰剂给药前1 h和给药后100 min进行，或在口服地尔硫卓30、60、90、120或180 mg后进行，在2 wk内的不同日期以单盲、交叉方式给药。地尔硫卓在60 mg以上剂量时延长心电图的P-R间期，但对FVC、FEV 1或FEF 25 -75无显著影响。平均值。+-。地尔硫卓给药后使FEV 1（PD 20）降低20%所需的乙酰甲胆碱剂量与地尔硫卓给药前PD 20的SEM比值，即，在任何剂量下，PD 20的倍数增加与安慰剂没有显著差异：0.93 ± 0.95。0.11安慰剂后，1.2 . ±. 0.1 30 mg后，1.3 ±。0.3 60 mg后，1.2 ±. 0.2 90 mg后，1.1 ±. 0.1 120 mg后，和1.0 ±. 0.1 180 mg.在标准化运动挑战前100分钟，以随机、双盲、交叉设计在至少间隔48小时的不同日期口服120至180 mg地尔硫卓和外观相同的安慰剂片剂。平均值。+-。运动后FEV 1的SEM最大降低为25.5 ± 0.001。安慰剂组为3.3%，安慰剂组为17.0 ±.地尔硫卓组为4.8%（P < 0.01）。FEV 1的变化与地尔硫卓或其活性代谢物去乙酰地尔硫卓的血药浓度无相关性。我们的结论是，口服地尔硫卓不会减弱气道反应乙酰甲胆碱或运动到临床上重要的程度，即使在剂量足以产生显着的心血管效应。
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, cross-over 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 < 0.01). There was no correlation between change in FEV1 and serum concentrations of diltiazem or its active metabolite desacetyldiltiazem. We conclude that oral diltiazem does not attenuate airway reactivity to methacholine or exercise to a clinically important degree, even at doses sufficient to produce significant cardiovascular effects.