van den Berg W, Leferink J G, Tabingh Suermondt W, Kreukniet J, Maes R A, Serra R, Bruynzeel P L
Int J Clin Pharmacol Ther Toxicol. 1983 Jan;21(1):24-30.
In eight asthmatic and six normal subjects serum terbutaline concentrations were correlated with changes in FEV1, MEF50%, Gaw, sGaw, and plasma cAMP concentrations after administration of 0.5 mg terbutaline subcutaneously, 5 mg orally, and an oral placebo. In asthmatics and normals the changes in serum terbutaline levels and plasma cAMP levels were closely correlated and in the same range. No change in lung function parameters was registered in normals, whereas in asthmatics a significant improvement was shown. In asthmatics all lung function parameters closely parallelled the changes in serum terbutaline concentrations and cAMP plasma concentrations, the FEV1 being the least variable lung function parameter. The maximal effect in FEV1 occurred 30-60 min after the subcutaneous dose and 2-4 h after the oral dose. The FEV1 improvement showed a linear relationship with the serum terbutaline concentration between 1.6 and 6 ng/ml. In contrast with theophyllines and anticholinergics, serum terbutaline concentrations showed a very low interindividual variance. Nevertheless it appeared that prediction of a certain improvement in lung function was not possible on the basis of the serum concentration. Since changes in plasma cAMP values after terbutaline therapy were similar in normals and asthmatics, the lung function improvement in the asthmatics suggests that if a beta-adrenergic defect exists, this must be mainly situated in the lung tissue.
对8名哮喘患者和6名正常受试者皮下注射0.5毫克特布他林、口服5毫克特布他林以及口服安慰剂后,测定其血清特布他林浓度,并将其与第一秒用力呼气容积(FEV1)、最大呼气中期流速(MEF50%)、气道导纳(Gaw)、比气道导纳(sGaw)以及血浆环磷腺苷(cAMP)浓度的变化进行相关性分析。在哮喘患者和正常受试者中,血清特布他林水平和血浆cAMP水平的变化密切相关且处于同一范围。正常受试者的肺功能参数未出现变化,而哮喘患者则表现出显著改善。在哮喘患者中,所有肺功能参数均与血清特布他林浓度和血浆cAMP浓度的变化密切平行,其中FEV1是变化最小的肺功能参数。皮下给药后30 - 60分钟以及口服给药后2 - 4小时,FEV1出现最大效应。FEV1的改善与血清特布他林浓度在1.6至6纳克/毫升之间呈线性关系。与茶碱类药物和抗胆碱能药物不同,血清特布他林浓度的个体间差异非常小。然而,似乎无法根据血清浓度预测肺功能的特定改善情况。由于特布他林治疗后正常受试者和哮喘患者的血浆cAMP值变化相似,哮喘患者肺功能的改善表明,如果存在β - 肾上腺素能缺陷,那么这种缺陷主要位于肺组织中。