Smit A J, Scaf A H, van Essen L H, Lie K I, Wesseling H
Department of Internal Medicine, University of Groningen, The Netherlands.
Eur J Clin Pharmacol. 1990;38(4):335-41. doi: 10.1007/BF00315571.
Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections, using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added. The validity of the simulations was tested in 11 patients with rapid atrial fibrillation. Serum digoxin concentrations, ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart. In agreement with the predictions of the model, the maximal fall in ventricular rate was reached after 8-9 h in the infusion group and after 19-20 h in the bolus injection group, without any detectable difference in side effects. There were certain discrepancies between the results of the clinical study and the predictions of the model, e.g. in serum digoxin concentrations, perhaps due to impaired clearance in the patients. However, it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation.
利用正常人时间-浓度和时间-效应关系的现有数据，采用三室药代动力学模型（随后增加了一个单独的小副作用室）模拟了不同时间段输注地高辛的结果，并与静脉推注地高辛的结果进行了比较。在11例快速心房颤动患者中对模拟的有效性进行了测试。在一项双盲研究中，监测了血清地高辛浓度、心室率和副作用，该研究比较了6小时内输注1.5毫克地高辛与间隔8小时静脉推注3次0.5毫克地高辛的情况。与模型预测一致，输注组在8-9小时后心室率降至最大，静脉推注组在19-20小时后心室率降至最大，副作用无任何可检测到的差异。临床研究结果与模型预测之间存在某些差异，例如血清地高辛浓度方面，可能是由于患者清除率受损所致。然而，得出的结论是，所测试的模型在老年快速心房颤动患者中是有效的。
