Gnocchi C A, Mazzocchi O, Yaryour C, Khoury M C, Noel M E, Torn A, Risso J A
Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires.
Medicina (B Aires). 1998;58(3):271-6.
In our country, patients with congestive heart failure who are treated chronically with digoxin are usually advised by their physicians to stop taking the medication two days a week. This is probably aimed at decreasing digitalis toxicity. Based on digoxin pharmacokinetics we assumed that the drug plasmatic level should diminish by 40 to 50%, below the therapeutic concentration of 0.8 to 2 milligrams, after two days of suspension. The objectives of this study were: a) to analyze the reduction of the plasmatic concentration of digoxin after a two day interruption of treatment, b) to compare the plasmatic levels of the drug between patients who received continuous and discontinuous treatment. A prospective, randomized and simple blind trial was designed. A total of 36 patients with congestive heart failure and systolic dysfunction with atrial fibrillation or sinus rythm were included. Group 1 (19 patients) received continuous treatment and Group 2 (17 patients) took the drug from Monday to Friday. In the continuous treatment group there was no significant difference between the Monday (1.06 +/- 0.55 milligrams) and the Friday (1.1 +/- 0.57 milligrams) digoxin concentrations. In the discontinuous treatment group the Monday digoxin concentration (0.611 +/- 0.396 milligrams) was lower than the Friday one (1.04 +/- 0.58 milligrams). The difference was statistically significant with a p = 0.000002. In conclusion, the two days a week suspension schedule reduces the plasmatic concentration of digoxin to subtherapeutic levels while the continuous regime maintains stable concentrations within the therapeutic range. Adjusting the dose to the creatinine clearance, average concentrations of 1 milligram are obtained. These results suggest that digitalis intoxication could be prevented by adjusting the dose according to renal function rather than interrupting the treatment as it is usually done in our country.
在我国,长期接受地高辛治疗的充血性心力衰竭患者,医生通常建议他们每周停药两天。这可能是为了降低洋地黄毒性。根据地高辛的药代动力学,我们假设停药两天后,药物血浆水平应降低40%至50%,降至0.8至2毫克的治疗浓度以下。本研究的目的是:a)分析治疗中断两天后地高辛血浆浓度的降低情况,b)比较接受连续和间断治疗患者的药物血浆水平。设计了一项前瞻性、随机且单盲试验。共纳入36例患有充血性心力衰竭且伴有房颤或窦性心律的收缩功能障碍患者。第1组(19例患者)接受连续治疗,第2组(17例患者)从周一至周五服药。连续治疗组周一(1.06±0.55毫克)和周五(1.1±0.57毫克)的地高辛浓度无显著差异。间断治疗组周一的地高辛浓度(0.611±0.396毫克)低于周五(1.04±0.58毫克)。差异具有统计学意义,p = 0.000002。总之,每周停药两天的方案可将地高辛血浆浓度降至亚治疗水平,而连续治疗方案可使浓度在治疗范围内保持稳定。根据肌酐清除率调整剂量,可获得平均浓度为1毫克的结果。这些结果表明,可通过根据肾功能调整剂量来预防洋地黄中毒,而不是像我国通常那样中断治疗。