Christie P E, Spur B W, Lee T H
Department of Allergy and Allied Respiratory Disorders, United Medical School, Guy's Hospital, London, England.
J Allergy Clin Immunol. 1991 Aug;88(2):193-8. doi: 10.1016/0091-6749(91)90328-l.
The effect of prior inhalation of the sulfidopeptide leukotriene receptor antagonist, SK&F 104353 (963 +/- 43.7 micrograms; mean +/- SEM), on (LTC4)- and leukotriene E4 (LTE4)-induced bronchoconstriction has been studied in six subjects with asthma (six male subjects, aged 24 to 36 years). Inhalation challenges with either synthetic LTC4 or LTE4 were performed after prior inhalation of aerosolized SK&F 104353 or placebo in a double-blind, randomized fashion. Airway responsiveness to each agonist was determined by the cumulative dose of agonist required to induce a 35% fall in specific airway conductance (PD35) as determined by linear interpolation of the log dose-response curve. There was no change in baseline specific airway conductance after inhalation of either placebo or SK&F 104353. LTC4- and LTE4-induced bronchoconstrictions were significantly inhibited by aerosolized inhalation of SK&F 104353 30 minutes before challenge. The geometric mean (GM) PD35 of LTC4 on the open-therapy and placebo-therapy days was 0.043 nmol (range, 0.01 to 0.1 nmol) and 0.036 nmol (range, 0.01 to 0.1 nmol), respectively. On the treatment day with SK&F 104353, it was not possible to obtain a GM PD35 LTC4 up to a maximum concentration of 0.52 nmol LTC4 (p less than 0.01). The GM PD35 of LTE4 on the open-therapy and placebo-therapy days was 0.30 nmol (range, 0.13 to 0.76 nmol) and 0.39 nmol (range, 0.14 to 0.9 nmol), respectively. On the treatment day with SK&F 104353, it was not possible to obtain a GM PD35 LTE4 up to a maximum concentration of 5 nmol LTE4 (p less than 0.005). Thus, LTC4- and LTE4-induced bronchoconstrictions are both inhibited by SK&F 104353.
在6名哮喘患者（6名男性，年龄24至36岁）中，研究了预先吸入硫肽白三烯受体拮抗剂SK&F 104353（963±43.7微克；平均值±标准误）对白三烯C4（LTC4）和白三烯E4（LTE4）诱导的支气管收缩的影响。在预先以双盲、随机方式吸入雾化的SK&F 104353或安慰剂后，用合成LTC4或LTE4进行吸入激发试验。通过对数剂量反应曲线的线性内插法确定诱导特定气道传导率下降35%所需的激动剂累积剂量（PD35），以此来测定气道对每种激动剂的反应性。吸入安慰剂或SK&F 104353后，基线特定气道传导率无变化。在激发试验前30分钟雾化吸入SK&F 104353可显著抑制LTC4和LTE4诱导的支气管收缩。开放治疗日和安慰剂治疗日LTC4的几何平均（GM）PD35分别为0.043纳摩尔（范围0.01至0.1纳摩尔）和0.036纳摩尔（范围0.01至0.1纳摩尔）。在使用SK&F 104353治疗的当天，直至LTC4最大浓度达到0.52纳摩尔时仍无法获得GM PD35（p<0.01）。开放治疗日和安慰剂治疗日LTE4的GM PD35分别为0.30纳摩尔（范围0.13至0.76纳摩尔）和0.39纳摩尔（范围0.14至0.9纳摩尔）。在使用SK&F 104353治疗的当天，直至LTE4最大浓度达到5纳摩尔时仍无法获得GM PD35（p<0.005）。因此，SK&F 104353可抑制LTC4和LTE4诱导的支气管收缩。
