Hedman A, Angelin B, Arvidsson A, Beck O, Dahlqvist R, Nilsson B, Olsson M, Schenck-Gustafsson K
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Clin Pharmacol Ther. 1991 Mar;49(3):256-62. doi: 10.1038/clpt.1991.26.
The interaction between digoxin and verapamil was studied in six patients (mean age +/- SD, 61 +/- 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 +/- 0.24 to 1.15 +/- 0.40 nmol/L (p less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 +/- 31 versus 173 +/- 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route.
对6例(平均年龄±标准差,61±5岁)慢性房颤患者进行了地高辛与维拉帕米相互作用的研究。采用交叉试验法,研究加用维拉帕米(240mg/天)对稳态血浆浓度以及地高辛肾清除率和胆汁清除率的影响。地高辛的胆汁清除率采用十二指肠灌注技术测定。维拉帕米使地高辛的稳态血浆浓度升高44%,从0.80±0.24nmol/L升至1.15±0.40nmol/L(p<0.01)。在使用维拉帕米的情况下,地高辛的胆汁清除率下降43%,从187±89ml/min降至101±55ml/min(p<0.05),而肾清除率未受影响(分别为153±31ml/min和173±51ml/min;差异无统计学意义)。我们的结果表明,维拉帕米对地高辛消除的主要抑制作用在于胆汁途径。