Meredith P A, Elliott H L, Pasanisi F, Kelman A W, Sumner D J, Reid J L
Br J Clin Pharmacol. 1985 Aug;20(2):101-6. doi: 10.1111/j.1365-2125.1985.tb05038.x.
The effect of acute and continued administration of verapamil on pharmacokinetics and regional blood flow has been studied in eight normotensive subjects. Continued administration resulted in a significant decrease in verapamil clearance, compared to that following acute dosing, as assessed by increases in both terminal elimination half-life (from a mean +/- s.d. of 5.2 +/- 2.3 h to 6.7 +/- 2.0 h) and AUC (from a mean +/- s.d. of 800 +/- 353 ng ml-1 h to 1455 +/- 244 ng ml-1 h). The relative clearance of norverapamil was not changed. Acute administration of verapamil resulted in a significant increase (P less than 0.005) in apparent liver blood flow which with continued administration fell significantly (P less than 0.01) towards placebo values. Effective renal plasma flow similarly increased with acute verapamil administration (P less than 0.05) and with chronic administration reduced again to be not significantly different from placebo. Acute and chronic verapamil administration did not significantly alter glomerular filtration rates. These results suggest that there may be a relationship between the acute increase in liver blood flow and the relatively increased clearance of verapamil following acute dosing.
在8名血压正常的受试者中研究了急性和持续给予维拉帕米对药代动力学和局部血流的影响。与急性给药后相比，持续给药导致维拉帕米清除率显著降低，这通过终末消除半衰期（从平均±标准差5.2±2.3小时增加到6.7±2.0小时）和AUC（从平均±标准差800±353 ng/ml·h增加到1455±244 ng/ml·h）的增加来评估。去甲维拉帕米的相对清除率没有变化。急性给予维拉帕米导致表观肝血流量显著增加（P<0.005），持续给药后则显著下降（P<0.01）至安慰剂值。有效肾血浆流量同样在急性给予维拉帕米时增加（P<0.05），慢性给药时再次降低至与安慰剂无显著差异。急性和慢性给予维拉帕米均未显著改变肾小球滤过率。这些结果表明，急性给药后肝血流量的急性增加与维拉帕米清除率相对增加之间可能存在关联。
