Taburet A M, Schmit B
Clinical Pharmacy, Hpital Bicêtre, Paris, France.
Clin Pharmacokinet. 1994 May;26(5):396-418. doi: 10.2165/00003088-199426050-00006.
Asthma is generally managed with bronchodilator therapy and/or anti-inflammatory drugs. Guidelines now advocate selection of drugs and pharmaceutical formulations (long-acting vs short-acting, inhaled vs systemic) on the basis of disease severity. Theophylline has a narrow therapeutic margin. Clearance is highly variable and plasma concentrations should be monitored to avoid the occurrence of plasma concentration-related adverse effects. The rate of absorption of theophylline differs depending on the sustained release formulation administered. Some products do not provide sufficient plasma drug concentrations for therapeutic efficacy over a 12-hour period, particularly in patients with high clearance rates (e.g. children and patients who smoke). Administration of drugs via inhalation offers several advantages over systemic routes of administration (e.g. adverse effects are decreased). Inhalation is now advocated as first-line therapy. Aerosol medications available for the treatment of asthma are beta 2-agonist (including the newer long-acting agents such as salmeterol), corticosteroids, anticholinergic drugs, sodium cromoglycate (cromolyn sodium) and nedocromil. To reach the airways, aerosolised particles should be 1 to 5 microns in diameter. Particles of this size can be produced by nebuliser for continuous administration or by metered-dose inhaler and drug powder inhaler for unit dose medication. For efficient use of the metered-dose inhaler, slow inhalation and actuation must be coordinated. However, efficacy and convenience can be improved when spacer devices are used. Furthermore, spacer devices lessen the oropharyngeal adverse effects of inhaled corticosteroids. Dry powder inhalers are more easily used by children and elderly patients than metered-dose inhalers. Regardless of the device used, a maximum of 10% of the inhaled dose reaches the airways. The rest of the dose is swallowed and absorbed through the gastrointestinal tract. Most inhaled drugs have low oral bioavailability, either because of a high first-pass metabolism (beta 2-agonists and glucocorticoids) or because of lack of absorption (sodium cromoglycate). Sulphation of beta 2-agonists occurs in the wall of the gastrointestinal tract and extensive metabolism of inhaled corticosteroids occurs in the liver. Low bioavailability of the swallowed fraction contributes to reduced adverse effects. The pharmacokinetic properties of an inhaled drug are of interest. The fraction of the dose absorbed through the lung has the same disposition characteristics as an intravenous dose, and the swallowed fraction has the same disposition as an orally administered dose. However, for many drugs, pharmacokinetic data after inhalation are limited and cannot be used as a criteria for selection of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
哮喘通常采用支气管扩张剂疗法和/或抗炎药物进行治疗。目前的指南提倡根据疾病严重程度选择药物和药物剂型（长效与短效、吸入与全身用药）。茶碱的治疗窗较窄。清除率差异很大，应监测血浆浓度以避免发生与血浆浓度相关的不良反应。茶碱的吸收速率因所用缓释剂型而异。一些产品在12小时内无法提供足够的血浆药物浓度以达到治疗效果，尤其是在清除率高的患者中（如儿童和吸烟者）。与全身给药途径相比，吸入给药具有多个优点（如不良反应减少）。现在提倡吸入疗法作为一线治疗。可用于治疗哮喘的气雾剂药物有β2激动剂（包括新型长效药物如沙美特罗）、皮质类固醇、抗胆碱能药物、色甘酸钠和奈多罗米。为了到达气道，雾化颗粒的直径应为1至5微米。这种大小的颗粒可通过雾化器连续给药产生，或通过定量吸入器和干粉吸入器进行单位剂量给药产生。为了有效使用定量吸入器，必须协调缓慢吸入和启动操作。然而，使用储物罐装置时，疗效和便利性可得到提高。此外，储物罐装置可减轻吸入性皮质类固醇的口咽不良反应。与定量吸入器相比，干粉吸入器更易于儿童和老年患者使用。无论使用何种装置，吸入剂量中最多只有10%能到达气道。其余剂量被吞咽并通过胃肠道吸收。大多数吸入药物的口服生物利用度较低，这要么是因为首过代谢率高（β2激动剂和糖皮质激素），要么是因为缺乏吸收（色甘酸钠）。β2激动剂在胃肠道壁发生硫酸化，吸入性皮质类固醇在肝脏发生广泛代谢。吞咽部分的低生物利用度有助于减少不良反应。吸入药物的药代动力学特性备受关注。经肺吸收的剂量部分具有与静脉注射剂量相同的处置特征，而吞咽部分具有与口服剂量相同的处置特征。然而，对于许多药物，吸入后的药代动力学数据有限，不能用作治疗选择的标准。（摘要截选至400字）
