Sweeney G D, MacLeod S M
McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
Clin Pharmacokinet. 1989;17 Suppl 1:156-68. doi: 10.2165/00003088-198900171-00011.
Six classes of drug may be prescribed in the treatment of airway hyperreactivity and allergy. Use of the methylxanthine theophylline requires that plasma drug concentrations be monitored because of its pharmacokinetic properties and narrow therapeutic range. beta 2-Selective adrenergic agonists, glucocorticoids, sodium cromoglycate and the quaternary antimuscarinic ipratopium achieve specificity of drug action on the bronchi with minimal side effects by local delivery as aerosols or 'microfine' powders. Glucocorticoids, sodium cromoglycate and ipratropium bromide may also be applied locally to the nasal mucosa in allergic rhinitis, and sodium cromoglycate (cromolyn sodium) may be applied to the eye. The 'antihistamines'--H1-receptor antagonists--are not used to treat bronchial hyperreactivity but are frequently used systemically for treating allergic conditions. Two new agents, terfenadine and astemizole, appear to be specific for H1-receptors and represent a new 'generation' of antihistamines that produce sedation only infrequently. Terfenadine exhibits a bimodal elimination phase (slow component +/- 22 hours) and astemizole has an active metabolite with a half-life of 12 days. The half-lives of most other antihistamines lie in the 4- to 8-hour range (except chlorpheniramine, which has a longer half-life). However, data reflecting disposition of these drugs in children are scanty. There is a need for more powerfully predictive pharmacokinetic approaches, which is discouraged by the widely used modelling approach combining patient and drug characteristics in single variables. Separation of these could improve extrapolation from drugs for which data are available to those for which they are not.
治疗气道高反应性和过敏时可开具六类药物。由于甲基黄嘌呤类药物氨茶碱的药代动力学特性及治疗窗较窄，使用时需要监测血浆药物浓度。β2 选择性肾上腺素能激动剂、糖皮质激素、色甘酸钠和季铵类抗胆碱能药物异丙托溴铵通过气雾剂或“微粉”形式局部给药，对支气管具有药物作用特异性且副作用最小。糖皮质激素、色甘酸钠和异丙托溴铵也可局部应用于变应性鼻炎的鼻黏膜，色甘酸钠（色甘酸二钠）可用于眼部。“抗组胺药”——H1 受体拮抗剂——不用于治疗支气管高反应性，但常用于全身性治疗过敏状况。两种新药特非那定和阿司咪唑似乎对 H1 受体具有特异性，代表了新一代抗组胺药，很少引起镇静作用。特非那定呈现双峰消除相（慢成分约±22 小时），阿司咪唑有一个半衰期为 12 天的活性代谢产物。大多数其他抗组胺药的半衰期在 4 至 8 小时范围内（氯苯那敏除外，其半衰期较长）。然而，关于这些药物在儿童体内处置情况的数据很少。需要更具预测性的药代动力学方法，而将患者和药物特征合并在单一变量中的广泛使用的建模方法并不支持这种需求。将这些因素分开可以改善从已有数据的药物推断到无相关数据药物的情况。
