Schmouder Robert, Serra Denise, Wang Yibin, Kovarik John M, DiMarco John, Hunt Thomas L, Bastien Marie-Claude
Exploratory Development, Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.
J Clin Pharmacol. 2006 Aug;46(8):895-904. doi: 10.1177/0091270006289853.
The purpose of this double-blind, placebo-controlled study was to measure the effects of FTY720, a novel immunomodulator, on heart rate and rhythm in healthy volunteers. Subjects (n = 66) were randomized to FTY720 1.25 mg or 5 mg or placebo administered once daily for 7 days. Continuous telemetry revealed an acute, dose-dependent decrease in mean heart rate (10-bpm decrease vs placebo) following the first dose of FTY720, with a nadir generally 4 hours postdose. Although a persistent FTY720-related decrease in heart rate was measured from day 2 to day 7, additional doses of FTY720 after day 2 resulted in no further incremental decreases. Mean PR interval increased by approximately 8 to 10 msec in FTY720-treated subjects on day 1. FTY720 did not increase the QRS or QT interval. These results confirm that the first dose of FTY720 has a mild to moderate negative chronotropic effect.
这项双盲、安慰剂对照研究的目的是测定新型免疫调节剂FTY720对健康志愿者心率和心律的影响。受试者（n = 66）被随机分为三组，分别每日服用一次1.25毫克或5毫克FTY720或安慰剂，持续7天。连续遥测显示，首次服用FTY720后，平均心率出现急性、剂量依赖性下降（与安慰剂相比下降10次/分钟），最低点通常出现在给药后4小时。尽管从第2天到第7天测量到FTY720相关的心率持续下降，但第2天后额外服用FTY720并未导致进一步的增量下降。在第1天，接受FTY720治疗的受试者的平均PR间期增加了约8至10毫秒。FTY720未增加QRS或QT间期。这些结果证实，首次服用FTY720具有轻度至中度的负性变时作用。
