Lauterburg B H
Schweiz Med Wochenschr. 1987 Mar 28;117(13):496-501.
The most frequently used calcium antagonists verapamil, diltiazem and nifedipine have common pharmacokinetic properties. Renal excretion of the drugs is minimal because of their lipophilicity, and the drugs are mainly metabolized by the liver. The rate of elimination depends not only on hepatic function but also on hepatic blood flow. Following oral administration only a fraction of the dose reaches the systemic circulation because of extensive first-pass metabolism. Elderly patients, patients with liver disease and patients in cardiac failure accompanied by decreased hepatic blood flow may experience untoward side effects that usually can be predicted by the known pharmacologic properties of the drugs, such as excessive vasodilatation following nifedipine and bradycardia and av-block following verapamil. Clinically important interactions with other drugs may result from inhibition of the metabolism of certain drugs (carbamazepine, cyclosporine, quinidine) by verapamil and/or diltiazem, inhibition of renal excretion (digoxin) by verapamil and diltiazem, and synergistic effects of beta blockers and verapamil.
最常用的钙拮抗剂维拉帕米、地尔硫䓬和硝苯地平具有共同的药代动力学特性。由于这些药物的亲脂性,其经肾排泄极少,主要在肝脏代谢。消除速率不仅取决于肝功能,还取决于肝血流量。口服给药后,由于广泛的首过代谢,只有一小部分剂量到达体循环。老年患者、肝病患者以及伴有肝血流量减少的心力衰竭患者可能会出现不良副作用,这些副作用通常可根据药物已知的药理特性预测,如硝苯地平后的过度血管扩张以及维拉帕米后的心动过缓和房室传导阻滞。与其他药物的临床重要相互作用可能源于维拉帕米和/或地尔硫䓬对某些药物(卡马西平、环孢素、奎尼丁)代谢的抑制、维拉帕米和地尔硫䓬对肾排泄(地高辛)的抑制以及β受体阻滞剂和维拉帕米的协同作用。