Keefe D L, Yee Y G, Kates R E
Clin Pharmacol Ther. 1981 Jan;29(1):21-6. doi: 10.1038/clpt.1981.4.
Verapamil plasma protein binding was studied in four groups of 12 subjects each: (1) normal subjects; (2) patients with moderate renal insufficiency and patients requiring dialysis; (3) patients 1 to 4 days after coronary artery surgery; and (4) patients undergoing cardiac catheterization. In normal subjects, plasma protein binding of verapamil was 89.6 +/- 0.17% and was concentration independent over a range of 35 to 1,557 ng/ml, which includes the usual clinical plasma range. In normal subjects, plasma protein binding of verapamil was not affected by addition of its major metabolite, norverapamil, in ratios of 1.2 to 26.3 (norverapamil/verapamil) or by the addition of 10 micrograms of warfarin. The plasma protein binding of verapamil was not altered in the postsurgical state or in the dialysis patients. Verapamil protein binding was initially lower in the cardiac catheterization patients (mean = 86.34 +/- 2.13%, p less than 0.001) than in normal subjects and was still lower (mean = 83.29 +/- 3.04%, p less than 0.02) after heparinization. There was also a small increase in binding in the patients with renal insufficiency (p less than 0.05). Plasma protein binding of verapamil in mongrel dogs (mean = 90.7%) was the same order. We found verapamil to be approximately 90% bound in man and dogs and not markedly changed by any of the conditions studied.
对四组每组12名受试者进行了维拉帕米血浆蛋白结合研究：（1）正常受试者；（2）中度肾功能不全患者和需要透析的患者；（3）冠状动脉手术后1至4天的患者；（4）接受心导管插入术的患者。在正常受试者中，维拉帕米的血浆蛋白结合率为89.6±0.17%，在35至1557 ng/ml的范围内与浓度无关，该范围包括通常的临床血浆范围。在正常受试者中，维拉帕米的血浆蛋白结合不受其主要代谢物去甲维拉帕米以1.2至26.3（去甲维拉帕米/维拉帕米）的比例添加或添加10微克华法林的影响。维拉帕米的血浆蛋白结合在术后状态或透析患者中未改变。心导管插入术患者中维拉帕米的蛋白结合最初低于正常受试者（平均值=86.34±2.13%，p<0.001），肝素化后仍较低（平均值=83.29±3.04%，p<0.02）。肾功能不全患者的结合也有小幅增加（p<0.05）。杂种犬中维拉帕米的血浆蛋白结合率（平均值=90.7%）处于同一水平。我们发现维拉帕米在人和犬中约90%被结合，并且在所研究的任何条件下均无明显变化。
