Jackson C, Lipworth B
Department of Clinical Pharmacology, University of Dundee.
Br J Gen Pract. 1995 Dec;45(401):683-7.
Successful management of asthmatic patients depends on achieving adequate delivery of inhaled drugs to the lung. This assumes particular importance for inhaled corticosteroids where the therapeutic goal should be to achieve a high ratio of airway anti-inflammatory efficacy to local and systemic side effects. The availability of user-friendly inhaler devices requires a critical appraisal of their effectiveness and an evaluation of whether improved lung deposition of anti-asthma drugs translates into improved clinical efficacy. There is evidence to suggest that the routine use of large-volume spacers for inhaled corticosteroids may not be the best first-line option, in that reduced drug delivery is associated with multiple actuations, inhalation delay and the presence of static electricity. Breath-actuated pressurized aerosol devices or dry powder inhaler devices may be a better option for many asthmatic patients, although the efficiency of drug delivery varies considerably between these devices. There is good evidence with a reservoir dry powder inhaler device to show that improved lung deposition translates into better therapeutic response, both in terms of beta 2-agonist and corticosteroid delivery. For inhaled corticosteroids, such as fluticasone propionate and budesonide, there is evidence to show that systemic bioactivity is mainly determined by lung bioavailability rather than gastrointestinal bioavailability, because of the absence of first-pass metabolism of these drugs in the lung. There is also evidence to show that the greater glucocorticoid potency of fluticasone propionate translates directly into greater systemic bioactivity, but not into enhanced efficacy, at doses above 1 mg daily. The use of efficient delivery systems, such as the reservoir dry powder inhaler device, may not only improve control of asthma and compliance with therapy, but may also allow dose reduction ('step-down' therapy) and hence may possibly reduce overall prescribing costs in the long term.
哮喘患者的成功管理取决于能否将吸入药物充分送达肺部。这对于吸入性糖皮质激素尤为重要，其治疗目标应是使气道抗炎疗效与局部及全身副作用的比例达到最佳。方便用户使用的吸入装置的可用性，需要对其有效性进行严格评估，并评估抗哮喘药物肺部沉积的改善是否能转化为临床疗效的提高。有证据表明，常规使用大容量储雾罐吸入糖皮质激素可能并非最佳的一线选择，因为多次按压、吸入延迟和静电的存在会导致药物递送减少。对于许多哮喘患者来说，呼吸驱动的压力定量气雾剂装置或干粉吸入装置可能是更好的选择，尽管这些装置之间的药物递送效率差异很大。有充分证据表明，对于储库型干粉吸入装置，无论是β2激动剂还是糖皮质激素的递送，肺部沉积的改善都能转化为更好的治疗反应。对于吸入性糖皮质激素，如丙酸氟替卡松和布地奈德，有证据表明，由于这些药物在肺部不存在首过代谢，全身生物活性主要由肺部生物利用度而非胃肠道生物利用度决定。也有证据表明，丙酸氟替卡松更高的糖皮质激素效力在每日剂量超过1毫克时直接转化为更大的全身生物活性，但并未转化为增强的疗效。使用高效递送系统，如储库型干粉吸入装置，不仅可以改善哮喘控制和治疗依从性，还可能允许减少剂量（“降级”治疗），从而从长远来看可能降低总体处方成本。
