Bottorff M B, Lalonde R L, Kazierad D J, Hoon T J, Tsiu S J, Mirvis D M
Division of Clinical and Hospital Pharmacy, University of Cincinnati, Ohio 45267.
Pharmacotherapy. 1989;9(5):315-21. doi: 10.1002/j.1875-9114.1989.tb04143.x.
The effects of diltiazem and encainide on the pharmacokinetics and metabolism of antipyrine were compared in nine healthy male volunteers. Diltiazem 90 mg every 8 hours for 5 days decreased the oral clearance of antipyrine from 2.34 to 1.86 L/hour (p less than 0.05) and increased half-life from 12.7 to 15.9 hours (p less than 0.05). Diltiazem reduced the formation rate constants for 3-hydroxymethylantipyrine by 27% (p less than 0.05) and 4-hydroxyantipyrine by 37% (p less than 0.05). There was also a 21% reduction in the formation rate constant for norantipyrine (0.05 less than p less than 0.10). Encainide 25 mg every 8 hours for 5 days had no apparent effect on the oral clearance or half-life of antipyrine, or on the formation rate constants for metabolites of antipyrine. In contrast to a previously published report in rats, encainide, unlike diltiazem, does not inhibit the oxidative metabolism of antipyrine in humans.
在9名健康男性志愿者中比较了地尔硫䓬和恩卡尼对抗吡咯药代动力学及代谢的影响。地尔硫䓬90毫克，每8小时1次，共5天，使安替比林的口服清除率从2.34升/小时降至1.86升/小时（p<0.05），半衰期从12.7小时延长至15.9小时（p<0.05）。地尔硫䓬使3-羟甲基安替比林的生成速率常数降低27%（p<0.05），使4-羟基安替比林的生成速率常数降低37%（p<0.05）。去甲安替比林的生成速率常数也降低了21%（0.05<p<0.10）。恩卡尼25毫克，每8小时1次，共5天，对安替比林的口服清除率、半衰期或安替比林代谢物的生成速率常数均无明显影响。与先前发表的关于大鼠的报告不同，与地尔硫䓬不同，恩卡尼不抑制人体中安替比林的氧化代谢。
