Sindrup S H, Gram L F, Skjold T, Frøland A, Beck-Nielsen H
Department of Clinical Pharmacology, Odense University, Denmark.
Clin Pharmacol Ther. 1990 Apr;47(4):509-15. doi: 10.1038/clpt.1990.65.
A single-blind imipramine dose titration study was conducted in 15 diabetic patients with neuropathy symptoms. The effect of treatment was evaluated by use of visual analog scales. Imipramine doses were individually adjusted until doses yielded plasma concentrations of imipramine plus desipramine that were well above 400 nmol/L or until all neuropathy symptoms had vanished. In all except one patient, there was marked relief of symptoms. In the responding patients (n = 14), much of the effect occurred at plasma levels of imipramine plus desipramine below 100 nmol/L, but a considerable interindividual variation was observed. Concentrations above 400 to 500 nmol/L were required to ensure maximal effect in all patients, and we did not find any indication of a decreased effect at high drug levels. The dose-dependent kinetics of imipramine was confirmed, and dose increments should therefore be carried out in small steps and preferably with monitoring of drug levels.
对15名有神经病变症状的糖尿病患者进行了一项单盲丙咪嗪剂量滴定研究。通过视觉模拟量表评估治疗效果。丙咪嗪剂量进行个体化调整，直至剂量产生的丙咪嗪加去甲丙咪嗪血浆浓度远高于400 nmol/L，或直至所有神经病变症状消失。除1名患者外，所有患者症状均明显缓解。在有反应的患者（n = 14）中，大部分效果出现在丙咪嗪加去甲丙咪嗪血浆水平低于100 nmol/L时，但观察到个体间存在相当大的差异。需要400至500 nmol/L以上的浓度才能确保所有患者达到最大效果，且我们未发现高药物水平时效果降低的任何迹象。证实了丙咪嗪的剂量依赖性动力学，因此剂量增加应以小步骤进行，最好监测药物水平。
