Influence of verapamil on the inotropism and pharmacokinetics of digoxin
Influence of verapamil on the inotropism and pharmacokinetics of digoxin
复制标题
维拉帕米对地高辛正性肌力作用和药代动力学的影响
DOI：
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发表时间：
2004
影响因子：
2.9
通讯作者：
F. Nielsen‐Kudsk
中科院分区：
文献类型：
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作者：
K. E. Pedersen;P. Thayssen;N. Klitgaard;B. D. Christiansen;F. Nielsen‐Kudsk
维拉帕米已被证实可抑制地高辛的消除，并使其稳态血浆浓度增加60%-80%。动物研究表明，维拉帕米取消了哇巴因和多巴胺等其他药物的内向作用。这种药物相互作用的临床后果是通过检查单剂量地高辛(从收缩时间间隔评估)的变力活性来研究的，其中包括联合使用和不联合使用维拉帕米。维拉帕米使地高辛的全身清除率从4.68±0.41降至3.29±0.26ml/min/kg(p<；0.001)，血浆半衰期从33.5±2.38增至41.31±2.27h(p<；0.01)。维拉帕米对心脏收缩间期的基线值无影响。在维拉帕米缺乏和存在的情况下，地高辛均可显著缩短总的机电收缩和左心室射血时间。然而，与对照条件相比，在维拉帕米存在的情况下，这些变化的衰减较慢，同时地高辛的血浆半衰期延长。在收缩时间间隔的缩短和计算机计算的深室地高辛浓度之间建立了线性关系。这些代表地高辛变力作用量效关系的回归线不受维拉帕米的影响。因此，维拉帕米本身对心脏基线收缩功能或地高辛诱发的变力作用都没有可测量的影响。维拉帕米引起的血浆地高辛浓度升高表现为变力作用。
SummaryVerapamil has been demonstrated to inhibit the elimination of digoxin and to increase its steady state plasma level by 60–80%. Animal studies suggest that verapamil abolishes the intropic action of other drugs such as ouabain and dopamine. The clinical consequences of this drug interaction were investigated by examining the inotropic activity of single doses of digoxin (assessed from systolic time intervals), with and without coadministration of verapamil. Verapamil decreased total-body clearance of digoxin from 4.68±0.41 to 3.29±0.26 ml/min/kg (p<0.001) and increased the plasma half-life of the drug from 33.50±2.38 to 41.31±2.27 h (p<0.01). Verapamil had no influence on the base-line values of the systolic time intervals. Both in the absence and presence of verapamil, digoxin caused significant shortening of the total electromechanical systole and the left ventricular ejection time. However, compared to control conditions, the decay of these changes was slower in the presence of verapamil, in parallel with the prolongation of the plasma half-life of digoxin. A linear relationship was established between reductions in the systolic time intervals and the computer-derived concentration of digoxin in the deep compartment. These regression lines, which represent the concentration-effect relationships of the inotropism of digoxin, were not affected by verapamil. Thus, verapamil per se had no measurable effect either on base-line contractile function of the heart or on digoxin-induced inotropism. The elevated plasma digoxin concentration induced by verapamil appears cardioactive in terms of inotropism.
维拉帕米对清醒狗左心房和心室正性肌力刺激的影响。
DOI：
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发表时间：
1982
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Goldman,S;Olajos,M;Morkin,E
通讯作者：
Morkin,E