Trial reportEuropean journal of clinical pharmacology2008
The effect on heart rate of combining single-dose fingolimod with steady-state atenolol or diltiazem in healthy subjects.
Trial report in European journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia.Anti-cancer drugs · 2016Pooled it
- Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study.Journal of neurology · 2014Trial
- Pharmacokinetic Variability of Direct Oral Anticoagulants and Calcium Channel Blockers: A Comparative Analysis of Exposure Data from Clinical Studies.Pharmaceutics · 2026Article
- Multiple Sclerosis and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study.Frontiers in immunology · 2022Article
- Pharmacokinetics and Tolerability of the Novel Non-immunosuppressive Fingolimod Derivative, OSU-2S, in Dogs and Comparisons with Data in Mice and Rats.The AAPS journal · 2020Article
- Review
- Review
- Unique catalytic activities and scaffolding of p21 activated kinase-1 in cardiovascular signaling.Frontiers in pharmacology · 2013Review
- Clinical pharmacokinetics of fingolimod.Clinical pharmacokinetics · 2012Review
- Benzofuran Derivatives as Potent, Orally Active S1P1 Receptor Agonists: A Preclinical Lead Molecule for MS.ACS medicinal chemistry letters · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe sphingosine-1-phosphate receptor modulator fingolimod (FTY720) is known to elicit a negative chronotropic effect at treatment initiation that attenuates over time with continued dosing. The authors determined the effect of combining a single dose of fingolimod with steady-state atenolol or diltiazem on heart rate and mean arterial pressure.
methodsIn a partially randomized, single-blind, placebo-controlled, three-period, crossover study, 25 healthy subjects received (1) a single oral 5-mg dose of fingolimod, (2) either 50 mg atenolol or 240 mg diltiazem once daily for 5 days, and (3) the antihypertensive for 5 days and a single dose of fingolimod on day 5. Telemetry and pharmacokinetic data were collected.
resultsThe daytime mean heart rate nadir was 15% lower when fingolimod was combined with atenolol (42 +/- 7 bpm) compared with fingolimod alone (51 +/- 9 bpm) yielding a combination/monotherapy ratio of 0.85 (90%CI, 0.79-0.92). The daytime mean heart rate nadir from fingolimod alone (55 +/- 5 bpm) was not altered when combined with diltiazem (56 +/- 8 bpm) yielding a ratio of 0.99 (0.94-1.05). There was no clinically relevant change in mean arterial pressure when fingolimod was administered with atenolol or diltiazem compared with administration of the drugs alone in normotensive subjects. The pharmacokinetics of the drugs were not altered during coadministration.
conclusionAdding fingolimod to a beta-blocker such as atenolol resulted in a moderately lower mean heart rate nadir compared with fingolimod alone. However, subjects who had a stronger negative chronotropic response to fingolimod alone (nadir < 50 bpm) had minimal or no further reduction in heart rate with the drug combination. Adding fingolimod to a calcium channel blocker such as diltiazem did not further lower the heart rate compared to fingolimod alone.
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Registered trials
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