Asgharnejad M, Powell J R, Donn K H, Danis M
School of Pharmacy, University of North Carolina, Chapel Hill 27514.
J Clin Pharmacol. 1988 Apr;28(4):339-43. doi: 10.1002/j.1552-4604.1988.tb03155.x.
Ten healthy male volunteers completed a study to determine the effect of cimetidine dose timing on the oral clearance of propranolol. Propranolol HCl 160 mg as tablets, was administered daily at 8 AM for 4 consecutive days on three occasions. In addition, cimetidine HCl 800 mg as tablets, was administered either simultaneously in the morning with propranolol (8 AM), at bedtime (10 PM), or not at all (control). Each treatment was separated by at least a 3-day washout. Propranolol and cimetidine serum samples were measured over the 24-hour dosing interval after the last propranolol dose. Cimetidine administration at 8 AM and 10 PM was associated with significant mean increases in the propranolol area under the serum concentration-time curve of 26% and 41%, respectively (P less than .002). The mean elimination half-life of propranolol was 6.3 hours during all three treatments. There was no significant difference in area under cimetidine serum concentration time curve between 8 AM and 10 PM dosing. Dosing cimetidine at bedtime 10 hours before propranolol does not diminish the magnitude of interaction.
十名健康男性志愿者完成了一项研究，以确定西咪替丁给药时间对普萘洛尔口服清除率的影响。将160毫克盐酸普萘洛尔制成片剂，连续4天每天上午8点给药，共进行三次。此外，将800毫克盐酸西咪替丁制成片剂，要么在上午与普萘洛尔同时给药（上午8点），要么在睡前（晚上10点）给药，要么根本不给药（对照）。每次治疗之间至少间隔3天的洗脱期。在最后一次普萘洛尔给药后的24小时给药间隔内测量普萘洛尔和西咪替丁的血清样本。上午8点和晚上10点给予西咪替丁分别使普萘洛尔血清浓度-时间曲线下面积平均显著增加26%和41%（P小于0.002）。在所有三种治疗中，普萘洛尔的平均消除半衰期为6.3小时。上午8点和晚上10点给药的西咪替丁血清浓度-时间曲线下面积没有显著差异。在普萘洛尔给药前10小时的睡前给予西咪替丁不会降低相互作用的程度。
