Hla K K, Henry J A, Latham A N
Poisons Unit, Guy's Hospital, London.
Br J Clin Pharmacol. 1987 Nov;24(5):661-4. doi: 10.1111/j.1365-2125.1987.tb03226.x.
The pharmacokinetics and pharmacodynamics of sustained release verapamil were compared with the conventional formulation in 10 healthy adult volunteers after single and multiple dosing. The mean time of maximum plasma concentrations of verapamil were significantly prolonged and the absorption rate constants significantly reduced after sustained release verapamil on both day 1 and day 10. On day 10 there was no significant difference between formulations in the relative bioavailability of verapamil. However, the area under the plasma concentration-time curve and maximum concentration (Cmax) for both formulations increased significantly with repeat dosing. On day 10, the difference in Cmax between formulations was significant. The day 10 mean peak/trough plasma verapamil concentration ratio was significantly less following the sustained release dose form. The mean PR interval was significantly prolonged by both formulations on day 1 and day 10. There were no differences between formulations other than a significantly longer PR interval following the conventional formulation 2 h after dosing on day 10.
在10名健康成年志愿者单次和多次给药后，对缓释维拉帕米与传统制剂的药代动力学和药效学进行了比较。在第1天和第10天，缓释维拉帕米给药后，维拉帕米的平均血浆浓度达峰时间显著延长，吸收速率常数显著降低。在第10天，两种制剂中维拉帕米的相对生物利用度无显著差异。然而，两种制剂的血浆浓度-时间曲线下面积和最大浓度（Cmax）均随重复给药而显著增加。在第10天，两种制剂的Cmax差异显著。在第10天，缓释剂型给药后，血浆维拉帕米平均峰谷浓度比显著降低。在第1天和第10天，两种制剂均使平均PR间期显著延长。除第10天给药2小时后传统制剂的PR间期显著更长外，两种制剂之间无其他差异。
