Nair Parameswaran, Hanrahan John, Hargreave Frederick E
Firestone Institute for Respiratory Health, St. Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Pol Arch Med Wewn. 2009 Nov;119(11):731-5.
There are no standardized methods to demonstrate in-vivo bioequivalence of inhaled bronchodilators. The most practical method of showing therapeutic equivalence in vivo is by estimating their relative potencies (RP) in clinical efficacy studies. The RP of bronchodilators may be estimated by comparing either their bronchodilator or bronchoprotective properties. Bronchodilator studies are easier to perform and may better model the physiologic effect of many agents, including inhaled beta-agonists. However, it may be difficult to demonstrate steep dose-response for these outcomes, except in cumulative study designs. Bioequivalence trials may be especially challenging when involving pressurized metered-dose inhalers, as a single actuation - the lowest feasible dose to include in the evaluation, may already produce bronchodilation that is at or near the plateau of the dose-response curve. Protection against bronchoconstriction induced by a direct inhaled stimulus like methacholine or histamine affords a reliable and practical method of comparing inhaled bronchodilators and estimating their RP. Inhalational bronchoprovocation testing allows for easier repeatability and quantitation of the stimulus necessary to produce a predetermined degree of bronchoconstriction, and the degree of protection afforded by the bronchoprotection agent. RP studies using adequate methodology are necessary to compare long-acting bronchodilators and both short- and long-acting bronchodilators in patients who are also on inhaled corticosteroids.
目前尚无标准化方法来证明吸入性支气管扩张剂的体内生物等效性。在体内显示治疗等效性的最实用方法是在临床疗效研究中评估它们的相对效价（RP）。支气管扩张剂的RP可以通过比较其支气管扩张或支气管保护特性来估计。支气管扩张剂研究更容易进行，并且可以更好地模拟许多药物（包括吸入性β受体激动剂）的生理效应。然而，除了在累积研究设计中，可能难以证明这些结果的陡峭剂量反应。当涉及压力定量吸入器时，生物等效性试验可能特别具有挑战性，因为单次喷雾——评估中可纳入的最低可行剂量，可能已经产生处于或接近剂量反应曲线平台的支气管扩张。针对由直接吸入刺激物（如乙酰甲胆碱或组胺）引起的支气管收缩的保护作用，提供了一种比较吸入性支气管扩张剂并估计其RP的可靠且实用的方法。吸入性支气管激发试验能够更轻松地重复产生预定程度支气管收缩所需的刺激，并能更轻松地定量支气管保护剂提供的保护程度。使用适当方法进行的RP研究对于比较长效支气管扩张剂以及同时使用吸入性糖皮质激素的患者中的短效和长效支气管扩张剂是必要的。
