Weinberger M, Hendeles L
Eur J Respir Dis Suppl. 1980;109:120-33.
Even with the availability of new and exciting antiasthmatic drugs, theophylline is emerging as one of the most useful noncorticosterioid agents available for suppressing symptoms in the patient with chronic asthma. Maximal benefit, however, requires appreciation of recent developments related to the pharmacodynamics and pharmacokinetics of theophylline. Serum theophylline concentrations between 10 and 20 microgram/ml are most likely to result in benefit without toxicity. A wide range of doses is required to attain these serum concentrations as a function of individual variability in the rate of drug elimination. Sustained-release theophylline preparations, when reliably and completely absorbed, offer major therapeutic advantage by minimizing fluctuations in serum concentrations and consequent variation in effect between doses. Moreover, this stabilization of the airway hyperreactivity of asthma can be attained with 12-hour dosing for most patients with one of the newer formulations. Initiation of therapy with low doses and determination of final dosage by measurement of serum theophylline concentration is essential for safe and effective use of this drug. Based upon cumulative frequency distributions, a simple and efficient dosing schedule had been developed that virtually eliminates problems of intolerance to the drug. About 99% of children and almost as many adults tolerate theophylline without adverse effects when used in this manner and most patients can be maintained virtually free of asthmatic symptoms with theophylline as the only chronic medication.
即使有了新型且令人振奋的抗哮喘药物，茶碱正成为可用于抑制慢性哮喘患者症状的最有用的非皮质类固醇药物之一。然而，要获得最大益处，需要了解与茶碱的药效学和药代动力学相关的最新进展。血清茶碱浓度在10至20微克/毫升之间最有可能产生益处而无毒性。由于药物消除速率存在个体差异，需要多种剂量才能达到这些血清浓度。当可靠且完全吸收时，缓释茶碱制剂通过最小化血清浓度波动以及剂量间效果的相应变化而提供主要治疗优势。此外，对于大多数使用新型制剂之一的患者，通过12小时给药可实现哮喘气道高反应性的稳定。低剂量开始治疗并通过测量血清茶碱浓度确定最终剂量对于安全有效地使用该药物至关重要。基于累积频率分布，已制定出一种简单有效的给药方案，几乎消除了对该药物不耐受的问题。以这种方式使用时，约99%的儿童和几乎同样多的成年人耐受茶碱而无不良反应，并且大多数患者仅使用茶碱作为唯一的慢性药物即可基本维持无哮喘症状。
