Richards R, Fowler C, Simpson S, Renwick A G, Holgate S T
Immunopharmacology Group, Southampton General Hospital.
Br J Clin Pharmacol. 1992 Mar;33(3):337-41. doi: 10.1111/j.1365-2125.1992.tb04048.x.
Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine challenge to determine the provocative concentration of histamine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20) from baseline. On two further visits they inhaled either saline placebo or histamine and 5 min later inhaled an aerosol containing sodium cromoglycate. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for 3 h. In the asthmatic group histamine inhalation led to a 24 +/- 4% reduction in FEV1 but had no effect on the normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways.
由于许多因素可能改变肺上皮对水溶性分子的通透性(LEP),因此在7名气道高反应性的轻度哮喘患者和8名正常受试者中研究了组胺对吸入色甘酸钠吸收和清除的影响。受试者接受组胺激发试验,以确定将一秒用力呼气容积(FEV1)从基线降低20%(PC20)所需的组胺激发浓度。在另外两次就诊时,他们吸入生理盐水安慰剂或组胺,5分钟后吸入含色甘酸钠的气雾剂。测量FEV1,并每隔一段时间采集血样分析血浆色甘酸钠浓度,持续3小时。在哮喘组中,吸入组胺导致FEV1降低24±4%,但对正常受试者无影响。与吸入生理盐水相比,组胺增加了色甘酸钠的初始肺吸收,而不影响哮喘患者和正常受试者吸收的药物总量。这些观察结果表明,气道药物吸收部位存在的炎症介质可能会显著改变吸入色甘酸钠的药代动力学。