Gupta S K, Yih B M, Atkinson L, Longstreth J
ALZA Corporation, Palo Alto, California 94303-0802, USA.
J Clin Pharmacol. 1995 Nov;35(11):1083-93. doi: 10.1002/j.1552-4604.1995.tb04031.x.
To evaluate the influence of food, time of dosing, and body position on the steady-state pharmacokinetics of an osmotically controlled formulation of verapamil (COER-verapamil), each of 29 healthy men received one tablet a day at specified times in an open-label, multiple-dose, four-period, crossover study. The verapamil tablets were administered in a randomized, balanced, crossover design: 240 mg at 8:00 AM on an empty stomach, subjects remaining ambulatory; 240 mg at 8:00 AM on an empty stomach, subjects remaining supine for 8 hours; 240 mg at 10:00 PM with a standardized meal, subjects remaining supine for 8 hours; and 240 mg at 10:00 PM on an empty stomach, subjects remaining supine for 8 hours. Plasma verapamil concentrations were measured at steady state over the dosing interval. Steady-state plasma concentrations were achieved by the fourth administration of the drug. Neither food nor posture had any effect on the pharmacokinetics of verapamil or norverapamil, or on hemodynamic measurements. Time of dosing did affect the rate of appearance and elimination of verapamil, but had no effect on the extent of verapamil absorption, norverapamil appearance, or hemodynamic measurements.
为评估食物、给药时间和体位对维拉帕米渗透泵控释制剂（COER-维拉帕米）稳态药代动力学的影响，在一项开放标签、多剂量、四周期、交叉研究中，29名健康男性在特定时间每天服用一片药。维拉帕米片采用随机、均衡、交叉设计给药：上午8点空腹服用240mg，受试者保持活动状态；上午8点空腹服用240mg，受试者仰卧8小时；晚上10点与标准餐同服240mg，受试者仰卧8小时；晚上10点空腹服用240mg，受试者仰卧8小时。在给药间隔内测定稳态时的血浆维拉帕米浓度。第四次给药后达到稳态血浆浓度。食物和体位对维拉帕米或去甲维拉帕米的药代动力学以及血流动力学测量均无影响。给药时间确实影响维拉帕米的出现和消除速率，但对维拉帕米的吸收程度、去甲维拉帕米的出现或血流动力学测量无影响。
