The effect on heart rate of combining single-dose fingolimod with steady-state atenolol or diltiazem in healthy subjects.
OBJECTIVE: 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 atenol...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 64; no. 5; pp. 457 - 464 |
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| Autores principales: | , , , , , , |
| Formato: | clinical trial research Journal Article |
| Publicado: |
Springer Nature
May2008
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105792086&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105792086 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: May2008 vid: 64 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105792086 2009880437 10.1007/s00228-007-0448-4 NLM18196225 105792086 ppf: 457 ppct: 7 formats: fmt: @attributes: type: P tig: atl: The effect on heart rate of combining single-dose fingolimod with steady-state atenolol or diltiazem in healthy subjects. aug: au: Kovarik JM Lu M Riviere GJ Barbet I Maton S Goldwater DR Schmouder RL sug: subj: Antihypertensive Agents Pharmacodynamics Atenolol Pharmacodynamics Diltiazem Pharmacodynamics Glycols Heart Rate Drug Effects Immunosuppressive Agents Pharmacodynamics Propylene Glycols Pharmacodynamics Adolescence Adult Antihypertensive Agents Pharmacokinetics Atenolol Pharmacokinetics Blood Pressure Monitoring, Ambulatory Blood Pressure Drug Effects Crossover Design Diltiazem Pharmacokinetics Female Glycols Pharmacodynamics Glycols Pharmacokinetics Immunosuppressive Agents Pharmacokinetics Male Middle Age Pharmacokinetics Propylene Glycols Pharmacokinetics Receptors, Cell Surface Metabolism Single-Blind Studies Human Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: OBJECTIVE: 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. METHODS: 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. RESULTS: 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 administration of the drugs alone in normotensive subjects. The pharmacokinetics of the drugs were not altered during coadministration. CONCLUSION: Adding 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. pubtype: Academic Journal doctype: clinical trial research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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