Pauwels R, Van der Straeten M
Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
J Allergy Clin Immunol. 1988 Apr;81(4):674-80. doi: 10.1016/0091-6749(88)91037-8.
The effect of ketotifen on bronchial beta-adrenergic tachyphylaxis was studied in healthy volunteers. In a 2-week pilot study, 19 volunteers inhaled 300 micrograms of salbutamol, four times a day. Ten subjects became tachyphylactic to inhaled salbutamol, assessed by a dose-response curve, before and after the 2 weeks of treatment from a metered-dose inhaler. These 10 subjects were then involved in a double-blind, crossover study comparing the effect of ketotifen, 1 mg in the evening during 1 week, and 1 mg, twice daily, during 3 weeks, and placebo on the bronchial beta-adrenergic tachyphylaxis induced by the concomitant administration during the last 2 weeks of each treatment period of 300 micrograms of salbutamol, four times a day, from a metered-dose inhaler. The end of the pilot study preceded the double-blind study by at least 1 month. However, the salbutamol dose-response curve at the beginning of the double-blind study was still significantly decreased, compared to the dose-response curve before the pilot study. During placebo treatment, a further decrease in bronchial beta-adrenergic sensitivity was observed. Treatment with ketotifen prevented the induction of further beta-adrenergic tachyphylaxis. Each 2 weeks of treatment with inhaled salbutamol increased significantly the baseline specific airway conductance; therefore, based on the present data, it is impossible to determine whether ketotifen also restores the sensitivity of an already desensitized beta-adrenergic system in the airways.
在健康志愿者中研究了酮替芬对支气管β-肾上腺素能快速减敏的作用。在一项为期2周的预试验研究中，19名志愿者每天4次吸入300微克沙丁胺醇。通过剂量反应曲线评估，10名受试者在使用定量吸入器进行2周治疗前后，对吸入沙丁胺醇产生了快速减敏。然后，这10名受试者参与了一项双盲交叉研究，比较酮替芬（在1周内每晚服用1毫克，在3周内每日服用2次，每次1毫克）和安慰剂对在每个治疗期最后2周每天4次从定量吸入器吸入300微克沙丁胺醇所诱导的支气管β-肾上腺素能快速减敏的影响。预试验研究结束至双盲研究开始至少间隔1个月。然而，与预试验研究前的剂量反应曲线相比，双盲研究开始时的沙丁胺醇剂量反应曲线仍显著降低。在安慰剂治疗期间，观察到支气管β-肾上腺素能敏感性进一步下降。酮替芬治疗可防止进一步诱导β-肾上腺素能快速减敏。每2周吸入沙丁胺醇治疗可显著增加基线比气道传导率；因此，根据目前的数据，无法确定酮替芬是否还能恢复气道中已经脱敏的β-肾上腺素能系统的敏感性。
