Keller F, Molzahn M, Ingerowski R
Eur J Clin Pharmacol. 1980 Nov;18(5):433-41. doi: 10.1007/BF00636799.
Previous dosing schedules for digoxin in renal failure have considered the decrease in the elimination rate constant but not the decrease in the volume of distribution. A dosing schedule based on the creatinine clearance, body weight and volume of distribution has been developed from pharmacokinetic data taken from the literature. Its validity was tested in a clinical study of 35 patients with chronic renal insufficiency not requiring dialysis. The dosing schedule resulted in correct digitalization expressed as a steady state plasma digoxin concentration in the therapeutic range (0.5-2.0 ng/ml) in 25 out of 27 patients (93%). However, of 82 possible candidates for the study, it could not be performed in 47 (57%). The high drop-out rate was mainly due to the complicated dosing schedule and to the difficulty of repeatedly measuring creatinine clearance on a routine basis. Therefore, safe dosing of digoxin in renal insufficiency does not seem to be feasible in practice. Digitoxin may be a better alternative.
以往针对肾衰竭患者的地高辛给药方案考虑了消除速率常数的降低，但未考虑分布容积的降低。根据从文献中获取的药代动力学数据，制定了一种基于肌酐清除率、体重和分布容积的给药方案。在一项针对35例无需透析的慢性肾功能不全患者的临床研究中对其有效性进行了测试。该给药方案使27例患者中的25例（93%）达到了正确的洋地黄化，表现为稳态血浆地高辛浓度处于治疗范围（0.5 - 2.0 ng/ml）。然而，在82名可能参与该研究的对象中，有47名（57%）无法纳入研究。高退出率主要是由于给药方案复杂，以及常规反复测量肌酐清除率存在困难。因此，在实际中，为肾功能不全患者安全给药地高辛似乎并不可行。洋地黄毒苷可能是更好的选择。
