Johnson J A, Akers W S
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Br J Clin Pharmacol. 1995 May;39(5):536-8. doi: 10.1111/j.1365-2125.1995.tb04492.x.
This study investigated the effect of verapamil metabolites on R- and S-verapamil protein binding in plasma samples collected from subjects prior to rac-verapamil dosing and following single dose and steady state rac-verapamil dosing. In vitro studies of the effects of norverapamil, D617 and D620 on R- and S-verapamil protein binding were also performed. Protein binding of R- and S-verapamil was unchanged following single and multiple doses of rac-verapamil as compared with protein binding in pre-dose samples. In vitro, norverapamil had no effect on R- and S-verapamil protein binding up to 1000 ng ml-1. Norverapamil 5000 ng ml-1 caused a 30% increase in free fraction of both R- and S-verapamil. D617 and D620 concentrations up to 5000 ng ml-1 had no effect on R- and S-verapamil protein binding. We conclude the metabolites of verapamil have no clinically significant effect on R- and S-verapamil protein binding.
本研究调查了维拉帕米代谢物对从受试者在消旋维拉帕米给药前、单次给药后和稳态消旋维拉帕米给药后采集的血浆样本中R-和S-维拉帕米蛋白结合的影响。还进行了去甲维拉帕米、D617和D620对R-和S-维拉帕米蛋白结合影响的体外研究。与给药前样本中的蛋白结合相比，单次和多次给予消旋维拉帕米后，R-和S-维拉帕米的蛋白结合未发生变化。在体外，高达1000 ng/ml的去甲维拉帕米对R-和S-维拉帕米的蛋白结合没有影响。5000 ng/ml的去甲维拉帕米使R-和S-维拉帕米的游离分数增加了30%。高达5000 ng/ml的D617和D620浓度对R-和S-维拉帕米的蛋白结合没有影响。我们得出结论，维拉帕米的代谢物对R-和S-维拉帕米的蛋白结合没有临床显著影响。
