Fleetham J A, Bird C E, Nakatsu K, Wigle R D, Munt P W
Thorax. 1981 May;36(5):382-6. doi: 10.1136/thx.36.5.382.
Dose-dependency in theophylline pharmacokinetics and protein binding characteristics was examined in 10 healthy male volunteers. Theophylline disposition was determined after an intravenous infusion of both 1 mg/kg and 6 mg/kg aminophylline in a randomised crossover study. There was considerable intrasubject variability in theophylline clearance but no significant dose-dependency. Theophylline protein binding was assessed by equilibrium dialysis at varying theophylline concentrations. The percentage of free non-protein bound theophylline was significantly increased at high theophylline concentrations. This increase in free theophylline would lead to a non-linear increase in the risk of toxicity with increasing drug concentration.
在10名健康男性志愿者中研究了茶碱药代动力学和蛋白质结合特性的剂量依赖性。在一项随机交叉研究中，静脉输注1mg/kg和6mg/kg氨茶碱后测定茶碱处置情况。茶碱清除率存在相当大的个体内变异性，但无显著剂量依赖性。通过在不同茶碱浓度下进行平衡透析评估茶碱蛋白结合情况。在高茶碱浓度下，游离非蛋白结合茶碱的百分比显著增加。随着药物浓度增加，游离茶碱的这种增加将导致毒性风险呈非线性增加。
