Koëter G H, Kraan J, Boorsma M, Jonkman J H, van der Mark T W
Department of Pulmonology, University Hospital, Groningen, The Netherlands.
Thorax. 1989 Dec;44(12):1022-6. doi: 10.1136/thx.44.12.1022.
The effect of increasing intravenous doses of theophylline and enprofylline, a new xanthine derivative, on bronchial responsiveness to methacholine was studied in eight asthmatic patients. Methacholine provocations were carried out on three days before and after increasing doses of theophylline, enprofylline, and placebo, a double blind study design being used. Methacholine responsiveness was determined as the provocative concentration of methacholine causing a fall of 20% in FEV1 (PC20). The patients were characterised pharmacokinetically before the main study to provide an individual dosage scheme for each patient that would provide rapid steady state plasma concentration plateaus of 5, 10, and 15 mg/l for theophylline and 1.25, 2.5, and 3.75 mg/l for enprofylline. Dose increments in the main study were given at 90 minute intervals. FEV1 showed a small progressive decrease after placebo; it remained high in relation to placebo after both drugs and this effect was dose related. Methacholine PC20 values decreased after placebo; mean values were higher after theophylline and enprofylline than after placebo (maximum difference 2.0 and 1.7 doubling doses of methacholine); the effect of both drugs were dose related. Thus enprofylline and theophylline when given intravenously cause a small dose related increase in FEV1 and methacholine PC20 when compared with placebo.
在八名哮喘患者中研究了增加静脉注射氨茶碱剂量以及一种新型黄嘌呤衍生物恩丙茶碱对支气管对乙酰甲胆碱反应性的影响。在增加氨茶碱、恩丙茶碱和安慰剂剂量之前及之后的三天进行乙酰甲胆碱激发试验，采用双盲研究设计。乙酰甲胆碱反应性以导致第一秒用力呼气容积（FEV1）下降20%的乙酰甲胆碱激发浓度（PC20）来确定。在主要研究之前对患者进行药代动力学特征分析，以便为每位患者提供个体化给药方案，使氨茶碱能快速达到5、10和15mg/l的稳态血药浓度平台，恩丙茶碱能达到1.25、2.5和3.75mg/l的稳态血药浓度平台。在主要研究中每隔90分钟增加一次剂量。安慰剂给药后FEV1呈小幅渐进性下降；两种药物给药后FEV1相对于安慰剂仍较高，且这种效应与剂量相关。安慰剂给药后乙酰甲胆碱PC20值下降；氨茶碱和恩丙茶碱给药后的平均值高于安慰剂给药后（最大差异为乙酰甲胆碱加倍剂量的2.0倍和1.7倍）；两种药物的效应均与剂量相关。因此，与安慰剂相比，静脉注射恩丙茶碱和氨茶碱会导致FEV1和乙酰甲胆碱PC20出现与剂量相关的小幅增加。
