Weinberger M, Hendeles L
Pediatr Pharmacol (New York). 1983;3(3-4):273-85.
Although theophylline has been available for over 50 years, only in the last 10 years has an understanding of its pharmacodynamics and pharmacokinetics permitted its use with optimal efficacy and safety. Serum concentrations between 10 and 20 mcg/ml stabilize the hyperreactive airways that characterize asthma as measured by exercise-induced bronchospasm and clinical suppression of asthmatic symptoms, even among those patients not sufficiently controlled with bronchodilators alone who consequently require inhaled or oral corticosteroid therapy. Careful dosage titration prevents adverse effects, especially when final dosage is guided by measurement of serum concentration. Large interpatient variability in dose requirements is seen, but there is normally little intrapatient variability except when physiologic abnormalities or drug interactions alter the elimination of theophylline. Rapid elimination, rapid absorption from conventional products, and the narrow therapeutic range for theophylline result in clinically important fluctuations in serum concentration and consequent effect unless unrealistically short dosing intervals are maintained or reliable slow-release formulations are used. Slow-release theophylline products vary, however, and performance often does not match the manufacturer's claims. Assessment requires characterization of absorption rate, which then allows prediction of fluctuations in serum concentration at specified dose intervals and defined rates of elimination.
尽管茶碱已问世50多年，但直到最近10年，对其药效学和药代动力学的了解才使其得以以最佳疗效和安全性使用。血清浓度在10至20微克/毫升之间可稳定哮喘所特有的高反应性气道，这可通过运动诱发性支气管痉挛和哮喘症状的临床抑制来衡量，即使在那些仅使用支气管扩张剂控制不佳、因此需要吸入或口服皮质类固醇治疗的患者中也是如此。仔细的剂量滴定可预防不良反应，尤其是当最终剂量以血清浓度测量为指导时。尽管患者之间的剂量需求存在很大差异，但通常患者自身的差异很小，除非生理异常或药物相互作用改变了茶碱的消除。茶碱的快速消除、传统产品的快速吸收以及狭窄的治疗范围，导致血清浓度出现具有临床意义的波动以及随之而来的效应，除非维持不切实际的短给药间隔或使用可靠的缓释制剂。然而，缓释茶碱产品各不相同，其性能往往与制造商的宣称不符。评估需要对吸收速率进行表征，进而能够预测在特定给药间隔和确定消除速率下血清浓度的波动情况。
