Risler T, Peters U, Grabensee B, Seipel L
Dtsch Med Wochenschr. 1979 Oct 26;104(43):1523-6. doi: 10.1055/s-0028-1129135.
After full digitalisation, 11 healthy subjects received 0.375 mg digoxin daily as maintenance dose. Under steady-state conditions and determination of serum concentration and renal clearance of digoxin, they were then given 500 or 1000 mg quinidine daily in addition to the digoxin. While serum concentration of digoxin rose significantly from 0.75 +/- 0.2 ng/ml after one week on 500 mg quinidine, and to 1.8 +/- 0.6 ng/ml after 1000 mg of quinidine, renal digoxin clearance fell from 186.2 +/- 67.4 to 125.4 +/- 61.8 ml/min after 500 mg of quinidine. Raising quinidine dosage to 1000 mg daily caused no further digoxin clearance reduction. During the total experimental period endogenous creatinine clearance remained unchanged. The results indicate that the rise in serum digoxin concentration on simultaneous quinidine administration is largely due to reduction in renal digoxin clearance. A clinical observation confirms the considerable practical importance of this interaction.
在完全数字化后,11名健康受试者每天接受0.375毫克地高辛作为维持剂量。在稳态条件下并测定地高辛的血清浓度和肾清除率后,除地高辛外,他们每天还额外给予500或1000毫克奎尼丁。当给予500毫克奎尼丁一周后,地高辛的血清浓度从0.75±0.2纳克/毫升显著升至1.8±0.6纳克/毫升,而给予1000毫克奎尼丁后,地高辛的血清浓度升至1.8±0.6纳克/毫升。给予500毫克奎尼丁后,地高辛的肾清除率从186.2±67.4毫升/分钟降至125.4±61.8毫升/分钟。将奎尼丁剂量提高到每天1000毫克并未进一步降低地高辛清除率。在整个实验期间,内源性肌酐清除率保持不变。结果表明,同时给予奎尼丁时血清地高辛浓度升高主要是由于地高辛肾清除率降低。一项临床观察证实了这种相互作用的相当大的实际重要性。