Barnes P J, Pride N B
Br J Clin Pharmacol. 1983 Jun;15(6):677-82. doi: 10.1111/j.1365-2125.1983.tb01549.x.
We have compared bronchodilator dose-response curves to inhaled salbutamol in seven normal and eight asthmatic subjects. In all normal subjects maximal bronchodilatation measured by partial flow volume curves was achieved at a cumulative dose of 110 micrograms. The dose necessary to produce half maximal response (ED50) was 23 +/- 2 micrograms (mean +/- s.e. mean) with a range of 18-28 micrograms. In asthmatic subjects maximal bronchodilatation measured by FEV1 and by maximal flow volume curves was achieved at significantly higher (P less than 0.01) doses of salbutamol with a mean ED50 of 83 +/- 28 micrograms and range of 25-251 micrograms. There was a significant (P less than 0.05) correlation between ED50 and % predicted baseline FEV1. This is more likely to reflect impaired access of drug for airway beta-adrenoceptors than impaired beta-adrenoceptor function in asthma. In five asthmatic subjects dose-response curves to salbutamol and isoprenaline were compared and found to be similar, thus providing no evidence that salbutamol is a partial agonist in vivo, as it appears to be in vitro.
我们比较了7名正常受试者和8名哮喘患者吸入沙丁胺醇后的支气管扩张剂剂量反应曲线。在所有正常受试者中,通过部分流量容积曲线测量的最大支气管扩张在累积剂量为110微克时达到。产生半数最大反应(ED50)所需的剂量为23±2微克(均值±标准误均值),范围为18 - 28微克。在哮喘患者中,通过FEV1和最大流量容积曲线测量的最大支气管扩张在显著更高(P<0.01)的沙丁胺醇剂量下实现,平均ED50为83±28微克,范围为25 - 251微克。ED50与预测的基线FEV1百分比之间存在显著(P<0.05)相关性。这更可能反映的是哮喘中药物进入气道β肾上腺素能受体的能力受损,而非β肾上腺素能受体功能受损。在5名哮喘患者中比较了沙丁胺醇和异丙肾上腺素的剂量反应曲线,发现它们相似,因此没有证据表明沙丁胺醇在体内是部分激动剂,尽管它在体外似乎是。