Ben-Dov I, Sue D Y, Hansen J E, Wasserman K
Am Rev Respir Dis. 1986 Jan;133(1):116-9. doi: 10.1164/arrd.1986.133.1.116.
The effect of a new dihydropyridine-derivative calcium antagonist, PY 108-068, on resting and postexercise flow rates was evaluated in 12 adult asthmatic subjects in a double-blind, randomized, placebo-controlled, cross-over study. The study consisted of 2 periods, each lasting for 3 days. For a given period a single dose of PY 108-068 (or placebo) was given orally, 75 mg on the first day and 150 mg on the second and third day. Spirometry was obtained at 30-min intervals thereafter. On Day 3, 75 min after the medication was given, a 6-min treadmill exercise test was performed breathing dry air. The mean maximal FEV1 recorded after 150 mg of PY 108-068 on Day 2 was 15 +/- 4% higher than the daily baseline (p less than 0.05), whereas after placebo the maximal FEV1 value was not different from the daily baseline. Also, the mean FEV1 values, expressed as percent of the daily predrug baseline, were significantly higher at 2 and 3 h after 150 mg of PY 108-068 than the respective values after placebo (110 +/- 4 compared with 95 +/- 1, and 106 +/- 5 compared with 91 +/- 3, respectively). Exercise-induced bronchospasm (EIB), expressed as maximal percent fall in FEV1 from preexercise baseline, was attenuated by PY 108-068 as compared with placebo (% delta FEV1 of 20 +/- 6 and 40 +/- 4, respectively; p less than 0.001). Protection against EIB did not correlate with the resting bronchodilation induced by PY 108-068, but was more likely if the patient had eosinophilia. Thus, PY 108-068 not only attenuates EIB but also causes resting bronchodilation, a unique finding for calcium channel blockers.
在一项双盲、随机、安慰剂对照、交叉研究中，对12名成年哮喘患者评估了一种新型二氢吡啶衍生物钙拮抗剂PY 108 - 068对静息和运动后流速的影响。该研究包括2个阶段，每个阶段持续3天。在给定阶段，口服单剂量的PY 108 - 068（或安慰剂），第一天75毫克，第二天和第三天150毫克。此后每隔30分钟进行一次肺功能测定。在第3天，给药75分钟后，进行6分钟的跑步机运动试验，呼吸干燥空气。第2天给予150毫克PY 108 - 068后记录的平均最大第一秒用力呼气量（FEV1）比每日基线高15±4%（p<0.05），而给予安慰剂后最大FEV1值与每日基线无差异。此外，以每日用药前基线的百分比表示的平均FEV1值，在给予150毫克PY 108 - 068后2小时和3小时显著高于给予安慰剂后的相应值（分别为110±4与95±1，以及106±5与91±3）。与安慰剂相比，PY 108 - 068减轻了运动诱发的支气管痉挛（EIB），以FEV1较运动前基线的最大下降百分比表示（分别为20±6和40±4；p<0.001）。对EIB的保护作用与PY 108 - 068诱导的静息支气管扩张无关，但如果患者有嗜酸性粒细胞增多则更有可能出现这种保护作用。因此，PY 108 - 068不仅减轻EIB，还能引起静息支气管扩张，这是钙通道阻滞剂的一个独特发现。
