Schenck-Gustafsson K, Dahlqvist R
Br J Clin Pharmacol. 1981 Feb;11(2):181-6. doi: 10.1111/j.1365-2125.1981.tb01122.x.
1 This study was designed to evaluate pharmacokinetically the digoxin-quinidine interaction in patients with atrial fibrillation. 2 Five patients on maintenance digoxin therapy were given [3H]-digoxin as a single i.v. dose before and during quinidine therapy and the elimination of [3H]-digoxin from plasma and excretion in urine were determined. 3 The mean steady state plasma concentration of digoxin increased from 0.7 to 1.3 nmol/l after quinidine administration. 4 The apparent volume of distribution of digoxin decreased on the average 38%. Renal clearance and the total body clearance of digoxin decreased 51 and 56% respectively (mean values). Also non renal clearance was reduced. The fraction of digoxin excreted unmetabolised in urine did not change during quinidine treatment. The mean elimination half life of digoxin increased from 49 to 72 h during quinidine. 5 In two patients the DC-shock did not cause a conversion to sinus rhythm. However, the quinidine induced changes in the pharmacokinetics of digoxin in these patients did not differ from the others. 6 Quinidine appears to decrease the amount of digoxin distributed to body tissue(s). In addition, the reduction of renal clearance of digoxin and the observed unchanged clearance of creatinine suggests an inhibition of the renal secretion of digoxin.
本研究旨在从药代动力学角度评估心房颤动患者中地高辛与奎尼丁的相互作用。
对5例接受地高辛维持治疗的患者,在奎尼丁治疗前及治疗期间静脉注射单次剂量的[3H]-地高辛,并测定血浆中[3H]-地高辛的消除及尿排泄情况。
服用奎尼丁后,地高辛的平均稳态血浆浓度从0.7纳摩尔/升增至1.3纳摩尔/升。
地高辛的表观分布容积平均减少38%。地高辛的肾清除率和总体清除率分别降低51%和56%(平均值)。非肾清除率也降低。奎尼丁治疗期间,尿液中未代谢排泄的地高辛比例未改变。地高辛的平均消除半衰期在服用奎尼丁期间从49小时增至72小时。
2例患者中直流电休克未导致转为窦性心律。然而,这些患者中奎尼丁引起的地高辛药代动力学变化与其他患者并无差异。
奎尼丁似乎会减少分布至身体组织的地高辛量。此外,地高辛肾清除率的降低以及观察到的肌酐清除率不变提示存在对地高辛肾分泌的抑制。