Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
Eur J Clin Pharmacol. 2012 Apr;68(4):355-62. doi: 10.1007/s00228-011-1146-9. Epub 2011 Nov 10.
Fingolimod (FTY720) is a sphingosine-1 phosphate-receptor (S1PR) modulator recently approved as a once-daily oral therapy for relapsing multiple sclerosis (MS) in many countries. As S1PRs are widely expressed, including in heart and lung tissues, this study investigated the possible effects of fingolimod on heart-rate circadian rhythm and pulmonary function.
Healthy volunteers (n = 39) were randomized to receive fingolimod 0.5 mg, 1.25 mg, or placebo for 14 days. Heart rate and measures of cardiac and pulmonary function were assessed during the study.
Mean heart rate for the first 12 h postdose was lower for both fingolimod than for placebo groups (p < 0.001) and remained 10-15 bpm lower than placebo until day 14 (p < 0.05). Heart rate circadian rhythm, cardiac output, stroke volume, and systemic vascular resistance were similar among treatment groups throughout the study. There was no evidence of an effect of fingolimod on pulmonary function. Absolute lymphocyte counts decreased by approximately 70% from baseline in both fingolimod groups (day 14) and began to increase within 14 days of stopping treatment.
In healthy volunteers treated for 14 days, once-daily fingolimod doses of 0.5 mg and 1.25 mg had no effect on cardiac or pulmonary function beyond a transient decrease in heart rate at treatment initiation.
芬戈莫德（FTY720）是一种鞘氨醇-1-磷酸受体（S1PR）调节剂，最近在许多国家被批准作为每日一次的口服疗法用于治疗复发型多发性硬化症（MS）。由于 S1PR 广泛表达，包括在心脏和肺部组织中，本研究调查了芬戈莫德对心率昼夜节律和肺功能的可能影响。
健康志愿者（n=39）随机接受芬戈莫德 0.5mg、1.25mg 或安慰剂治疗 14 天。在研究期间评估心率和心脏及肺功能的测量值。
与安慰剂组相比，芬戈莫德组首次给药后 12 小时内的平均心率更低（p<0.001），直至第 14 天仍比安慰剂组低 10-15bpm（p<0.05）。心率昼夜节律、心输出量、每搏量和全身血管阻力在整个研究期间在各组之间相似。芬戈莫德对肺功能没有影响的证据。在两个芬戈莫德组中（第 14 天），淋巴细胞计数从基线下降了约 70%，并在停止治疗后 14 天内开始增加。
在接受 14 天治疗的健康志愿者中，每日一次的芬戈莫德剂量为 0.5mg 和 1.25mg，除了在治疗开始时心率短暂下降外，对心脏或肺功能没有影响。
