Lipworth B J, Newnham D M, Clark R A, Dhillon D P, Winter J H, McDevitt D G
Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, UK.
Thorax. 1995 Jan;50(1):54-61. doi: 10.1136/thx.50.1.54.
There is controversy as to the relative safety of fenoterol and salbutamol. No differences have been found in the relative cardiac beta 1/beta 2 receptor activity of inhaled fenoterol and salbutamol in normal subjects. These initial findings have been extended by comparing the respective potencies of equivalent doses by weight of fenoterol and salbutamol in asthmatic subjects, in terms of airways and systemic responses.
Eighteen asthmatic patients of mean (SD) age 40 (14) years and a forced expiratory volume in one second (FEV1)% predicted of 56 (14)% (1.97 (0.66)1) were randomised to inhale fenoterol (100 micrograms/puff or 200 micrograms/puff), salbutamol, or placebo (100 micrograms/puff or 200 micrograms/puff) on three separate days. Dose-response curves were constructed using cumulative doses of 100 micrograms, 200 micrograms, 400 micrograms, 1000 micrograms, 2000 micrograms, and 4000 micrograms, and airways and systemic responses were measured 20 minutes after each dose with 40 minute increments. Dose ratios for the relative potency of fenoterol versus salbutamol were calculated from the dose-response curves using regression analysis of parallel slopes.
There was no difference in bronchodilator potency between fenoterol and salbutamol (as median dose ratio): FEV1 1.1 (95% CI 0.4 to 4.6). In contrast, dose ratios for systemic responses showed that fenoterol was more potent than salbutamol: serum potassium 3.7 (95% CI 2.0 to 6.0), tremor 5.7 (95% CI 1.4 to 10.2), heart rate 1.6 (95% CI 1.0 to 2.3). At a conventional dose of 200 micrograms the only difference in response between the two drugs was observed for tremor (as mean difference): 0.23 log units (95% CI 0.06 to 0.41 log units).
There was no difference in the bronchodilator potency between fenoterol and salbutamol on a microgram equivalent basis. In contrast, systemic potency was greater with fenoterol, although this difference was not clinically relevant at conventional dosages up to 200 micrograms.
非诺特罗和沙丁胺醇的相对安全性存在争议。在正常受试者中,吸入非诺特罗和沙丁胺醇后,心脏β1/β2受体的相对活性未发现差异。通过比较非诺特罗和沙丁胺醇按重量计等效剂量在哮喘患者中的气道和全身反应的各自效价,对这些初步发现进行了扩展。
18例哮喘患者,平均(标准差)年龄40(14)岁,一秒用力呼气容积(FEV1)占预计值的百分比为56(14)%(1.97(0.66)升),随机分为三组,在三个不同日期分别吸入非诺特罗(100微克/喷或200微克/喷)、沙丁胺醇或安慰剂(100微克/喷或200微克/喷)。使用100微克、200微克、400微克、1000微克、2000微克和4000微克的累积剂量构建剂量-反应曲线,每次给药后20分钟测量气道和全身反应,每次测量间隔40分钟。使用平行斜率回归分析从剂量-反应曲线计算非诺特罗与沙丁胺醇相对效价的剂量比。
非诺特罗和沙丁胺醇的支气管扩张效价无差异(中位数剂量比):FEV1为1.1(95%可信区间0.4至4.6)。相比之下,全身反应的剂量比表明非诺特罗比沙丁胺醇更有效:血清钾为3.7(95%可信区间2.0至6.0),震颤为5.7(95%可信区间1.4至10.2),心率为1.6(95%可信区间1.0至2.3)。在200微克的常规剂量下,两种药物之间仅在震颤方面观察到反应差异(平均差异):0.23对数单位(95%可信区间0.06至0.41对数单位)。
以微克当量为基础,非诺特罗和沙丁胺醇的支气管扩张效价无差异。相比之下,非诺特罗的全身效价更高,尽管在高达200微克的常规剂量下这种差异在临床上并不相关。