Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusions
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.
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Acknowledgments
The authors take full responsibility for the content of the paper but thank Sarah Griffiths, Rowena Hughes, and Eric Southam (Oxford PharmaGenesis™ Ltd) for editorial assistance, collating the comments of authors and other named contributors, and editing the paper for submission. The authors are grateful for the technical contributions of Thomas Dumortier.
Conflict of interest disclosure
This study was supported by Novartis Pharmaceuticals Corporation, New Jersey, USA.
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Schmouder, R., Hariry, S. & David, O.J. Placebo-controlled study of the effects of fingolimod on cardiac rate and rhythm and pulmonary function in healthy volunteers. Eur J Clin Pharmacol 68, 355–362 (2012). https://doi.org/10.1007/s00228-011-1146-9
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DOI: https://doi.org/10.1007/s00228-011-1146-9