Lötvall J
Department of Respiratory Medicine and Allergology, Göteborg University, Sweden.
Respir Med. 2001 Aug;95 Suppl B:S7-11. doi: 10.1053/rmed.2001.1139.
Formoterol and salmeterol are both long-acting bronchodilators that are effective in the treatment of asthma. However, some differences exist in their pharmacology that are reflected in their clinical profiles. Formoterol has a rapid onset of action, whereas salmeterol causes bronchodilation in a somewhat slower manner. However, both ofthese drugs are long-acting. After single doses clear effects are maintained for 12 h after inhalation, and with high doses effects are observed even at 24 h. Differences between the maximal effects of both drugs are also a consequence of their pharmacological properties. Thus, formoterol has higher intrinsic activity than salmeterol, which means that it is a full agonist, whereas salmeterol is a partial agonist on the beta2-receptor. Physicochemical properties of the drugs may explain the differences in onset and duration of action. Adequate water solubility and moderate lipophilicity of formoterol ensures rapid diffusion to the beta2-receptor on the smooth muscle and rapid bronchodilating activity. Salmeterol, on the other hand, may diffuse more slowly to the beta2-receptor because of its high lipophilicity explaining the slower onset of action. Unlike salbutamol, which is hydrophilic and has a rapid onset and short duration of action, both formoterol and salmeterol possess adequate lipophilic properties to remain in the airway tissues as a depot in close vicinity to the beta2-receptor, explaining their long duration of effect. The long duration of salmeterol has also been suggested to depend on an anchored binding within the beta2-receptor. The pharmacological evidence for a rapid onset of action of formoterol, but long duration of effect, is supported by several clinical studies. The fast onset of bronchodilation and high intrinsic activity of formoterol therefore suggest that it can be used for relief treatment in patients with asthma if they are concomitantly treated with inhaled glucocorticoids.
福莫特罗和沙美特罗都是长效支气管扩张剂，对哮喘治疗有效。然而，它们的药理学存在一些差异，这在它们的临床特征中有所体现。福莫特罗起效迅速，而沙美特罗引起支气管扩张的方式则稍慢。然而，这两种药物都是长效的。单次给药后，吸入后12小时可维持明显效果，高剂量时甚至在24小时仍可观察到效果。两种药物最大效果的差异也是其药理学特性的结果。因此，福莫特罗比沙美特罗具有更高的内在活性，这意味着它是一种完全激动剂，而沙美特罗是β2受体的部分激动剂。药物的物理化学性质可能解释了起效和作用持续时间的差异。福莫特罗足够的水溶性和适度的亲脂性确保其迅速扩散到平滑肌上的β2受体并具有快速的支气管扩张活性。另一方面，沙美特罗因其高亲脂性可能向β2受体扩散得更慢，这解释了其起效较慢的原因。与亲水性、起效迅速且作用持续时间短的沙丁胺醇不同，福莫特罗和沙美特罗都具有足够的亲脂性，能够作为储库留在气道组织中，紧邻β2受体，这解释了它们作用持续时间长的原因。沙美特罗作用持续时间长也被认为取决于其在β2受体内的锚定结合。多项临床研究支持了福莫特罗起效迅速但作用持续时间长的药理学证据。因此，福莫特罗快速的支气管扩张起效和高内在活性表明，如果同时给予吸入性糖皮质激素治疗，它可用于哮喘患者的缓解治疗。
