Abstract
The 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. In 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. The 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 admi...Continue Reading
References
Jun 1, 1979·Drugs·R C HeelG S Avery
May 1, 1982·Pharmacotherapy·B J McAuley, J S Schroeder
Aug 17, 2002·Current Opinion in Immunology·Volker Brinkmann, Kevin R Lynch
Apr 20, 2004·British Journal of Clinical Pharmacology·John M KovarikGerolf Kraus
Dec 1, 2004·Therapeutic Drug Monitoring·John M KovarikAlan J Slade
Dec 13, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lev KoyrakhKevin Wickman
Jul 21, 2006·Journal of Clinical Pharmacology·Robert SchmouderMarie-Claude Bastien
Sep 15, 2006·The New England Journal of Medicine·Ludwig KapposUNKNOWN FTY720 D2201 Study Group
Jan 2, 2007·Transplantation·Helio Tedesco-SilvaUNKNOWN FTY720 Study Group
Citations
Dec 14, 2011·Clinical Pharmacokinetics·Olivier J DavidRobert L Schmouder
Aug 13, 2015·Multiple Sclerosis and Related Disorders·John P DiMarcoLudwig Kappos
Jul 27, 2014·Drugs·Mark Sanford
Jul 22, 2014·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·H RoshanisefatS Montgomery
Dec 9, 2014·European Journal of Medicinal Chemistry·Hena Khanam, Shamsuzzaman
Nov 14, 2013·Journal of Neurology·Ralf GoldUNKNOWN FIRST Study Investigators
Jun 2, 2016·Expert Opinion on Drug Metabolism & Toxicology·Pierre-Eric JuifJasper Dingemanse
Jun 25, 2014·Multiple Sclerosis : Clinical and Laboratory Research·S RossiD Centonze
Mar 17, 2017·Fundamental & Clinical Pharmacology·Sylvie PiloteBenoit Drolet
Mar 31, 2016·Current Opinion in Neurology·Divyanshu DubeyOlaf Stüve
Apr 14, 2017·CNS Drugs·Peer Tfelt-HansenJacob Tfelt-Hansen
Aug 26, 2016·Journal of Clinical Pharmacology·Pierre-Eric JuifJasper Dingemanse
Mar 12, 2016·Anti-cancer Drugs·Anoop K EnjetiPhilip Rowlings
Jul 18, 2020·The AAPS Journal·Zhiliang XieMitch A Phelps
Feb 10, 2011·ACS Medicinal Chemistry Letters·Ashis K SahaHan Xu
Apr 17, 2012·Journal of Medicinal Chemistry·Feng RenXichen Lin