Drotar D E, Davis E E, Cockcroft D W
Department of Medicine, Royal University Hospital, Saskatoon, Canada.
Ann Allergy Asthma Immunol. 1998 Jan;80(1):31-4. doi: 10.1016/S1081-1206(10)62935-3.
Regular use of salmeterol has been associated with reduced bronchoprotective effect against methacholine as early as 24 hours after initiating treatment.
To determine whether loss of the bronchoprotective effect measured one hour after salmeterol could be demonstrated 12 hours following one previous dose.
Ten subjects with stable, mild asthma were enrolled in a randomized, placebo-controlled, double-blind, crossover study comparing two 2-dose treatment periods: (1) blinded salmeterol 50 microg inhaled at bedtime, followed by unblinded salmeterol 50 microg inhaled 12 hours later and (2) blinded placebo inhaled at bedtime, followed by unblinded salmeterol 50 microg inhaled 12 hours later. The methacholine PC20 was measured one hour after the morning salmeterol; FEV1 was measured just prior to the morning salmeterol dose and at the start of the methacholine inhalation test.
The mean log methacholine PC20 recorded one hour after a single dose of salmeterol (1.20 +/- 0.17 SE) was significantly higher than the mean log methacholine PC20 recorded after two doses of salmeterol at 12-hour intervals (1.00 +/- 0.16 SE; P = .024). The mean FEV1 12 hours after salmeterol was significantly higher than the mean FEV1 recorded 12 hours after placebo (P = .0017), however, there was no significant difference between the FEV1 recordings one hour after the two unblinded doses of salmeterol.
Tolerance to the bronchoprotective effect of salmeterol against methacholine induced bronchoconstriction occurs extremely quickly as it is evident 12 hours after starting twice daily treatment.
早在开始使用沙美特罗治疗24小时后，规律使用沙美特罗就与对乙酰甲胆碱的支气管保护作用降低有关。
确定在之前一剂用药12小时后，能否证明沙美特罗用药1小时后所测得的支气管保护作用丧失。
10名病情稳定的轻度哮喘患者参加了一项随机、安慰剂对照、双盲、交叉研究，比较两个2剂治疗期：（1）睡前吸入盲法给予的50微克沙美特罗，12小时后吸入非盲法给予的50微克沙美特罗；（2）睡前吸入盲法给予的安慰剂，12小时后吸入非盲法给予的50微克沙美特罗。在早晨吸入沙美特罗1小时后测量乙酰甲胆碱PC20；在早晨吸入沙美特罗剂量前及乙酰甲胆碱吸入试验开始时测量第一秒用力呼气量（FEV1）。
单次剂量沙美特罗用药1小时后记录的平均对数乙酰甲胆碱PC20（1.20±0.17标准误）显著高于每隔12小时给予两剂沙美特罗后记录的平均对数乙酰甲胆碱PC20（1.00±0.16标准误；P = 0.024）。沙美特罗用药12小时后的平均FEV1显著高于安慰剂用药12小时后记录的平均FEV1（P = 0.0017），然而，两次非盲法给予沙美特罗剂量1小时后的FEV1记录之间无显著差异。
沙美特罗对乙酰甲胆碱诱导的支气管收缩的支气管保护作用耐受性出现极快，因为在每日两次治疗开始12小时后就很明显了。
