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Carolyn R Sikes - One of the best experts on this subject based on the ideXlab platform.

  • patient satisfaction with Eletriptan in the acute treatment of migraine in primary care
    International Journal of Clinical Practice, 2007
    Co-Authors: Robert Nett, Mary Almas, P J Tiseo, Carolyn R Sikes
    Abstract:

    SUMMARY Objective: The efficacy of triptans for acute migraine has been well established in clinical trials but not in primary care, where they are most commonly prescribed. The aim of this open-label study was to evaluate the effectiveness of Eletriptan 40 mg in primary care, using a patient-weighted satisfaction scale. Methods: Eligible patients met International Headache Society criteria for migraine, with 1‐6 attacks per month. Patients completed questionnaires at screening and following a single Eletriptan-treated attack. Treatment satisfaction was evaluated using a sixitem Medication Satisfaction Questionnaire (MSQ). MSQ item scores were weighted, based on the important score ratings, to yield individualised satisfaction scores. The primary end-point was the difference in weighted satisfaction scores between the patient’s previous treatment and Eletriptan 40 mg. Secondary endpoints assessed quality of life (QOL), functioning and efficacy of treatment. Results: Of 590 patients screened, 437 completed the study. Degree (95.2%), time (88.8%) and duration (83.8%) of headache pain relief were rated as most important by patients. The mean (±SD) total satisfaction score on the MSQ was higher for Eletriptan than previous therapy (2.2 ± 3.0 vs. 0.6 ± 2.4; p < 0.001). The high level of satisfaction with Eletriptan vs. previous treatment reflects the improvements in QOL and functioning observed, and the high headache and painfree response rates. Conclusions: Patient-weighted satisfaction with Eletriptan 40 mg was higher than with previous treatment for all items. The use of patientweighted importance ratings of satisfaction is a promising approach for establishing effectiveness of treatment in primary care. What’s known The efficacy of triptans (5-HT1B/1D-receptor agonists) has been well established in clinical trials, but not in a primary care setting, where they are most commonly prescribed. Previous studies have highlighted the treatment outcomes that are most important to migraine sufferers (e.g. degree of pain relief, speed of relief and duration of relief). Asking patients to rate their treatment in terms of the treatment outcomes that are most important to them has been suggested as a useful way of assessing the effectiveness of a treatment in primary care. What’s new

  • Efficacy of Eletriptan in Triptan‐Naïve Patients: Results of a Combined Analysis
    Headache, 2007
    Co-Authors: Vincent T Martin, Jayasena Hettiarachchi, Carolyn R Sikes, Mary Almas, Dominique Valade, Kenneth S Albert, Bruce Parsons
    Abstract:

    OBJECTIVE: To compare the efficacy and tolerability of Eletriptan 20 mg, 40 mg, and 80 mg in triptan-naive patients (who have not previously used triptans) versus triptan-experienced patients (who have previously used triptans). METHODS: Efficacy and tolerability data for Eletriptan 20 mg, 40 mg, and 80 mg were pooled from 10 similarly designed, randomized, parallel-group studies, and triptan-naive and triptan-experienced patients were compared with placebo across the 3 triptan doses. The primary efficacy endpoint was headache response at 2 hours postdose. Secondary efficacy endpoints were 2-hour pain-free response, 2-hour absence of associated symptoms, 2-hour functional response, 24-hour sustained headache response, and 24-hour sustained pain-free response. RESULTS: For Eletriptan 20 mg, 40 mg, and 80 mg versus placebo, respectively, triptan-naive patients showed significantly higher 2-hour headache response (54%, 61%, 66% vs. 31%; P < .0001), 2-hour pain-free response (20%, 28%, and 31% vs. 8%; P < .0001), and 24-hour sustained headache response (34%, 45%, and 51% vs. 20%; P < .0001). A similarly significant efficacy advantage was also observed in the triptan-experienced subgroup for 2-hour headache response (46%, 63%, 69% vs. 21%; P < .0001), 2-hour pain-free response (13%, 32%, and 38% vs. 4%; P < .0001), and 24-hour sustained headache response (29%, 41%, and 45% vs. 9%; P < .0001). Previous treatment status did not influence tolerability, and all 3 doses of Eletriptan were well tolerated. CONCLUSIONS: These data suggest that Eletriptan has comparable efficacy versus placebo among both triptan-naive and triptan-experienced patients.

  • efficacy of Eletriptan in triptan naive patients results of a combined analysis
    Headache, 2007
    Co-Authors: Vincent T Martin, Jayasena Hettiarachchi, Carolyn R Sikes, Mary Almas, Dominique Valade, Kenneth S Albert, Bruce Parsons
    Abstract:

    OBJECTIVE: To compare the efficacy and tolerability of Eletriptan 20 mg, 40 mg, and 80 mg in triptan-naive patients (who have not previously used triptans) versus triptan-experienced patients (who have previously used triptans). METHODS: Efficacy and tolerability data for Eletriptan 20 mg, 40 mg, and 80 mg were pooled from 10 similarly designed, randomized, parallel-group studies, and triptan-naive and triptan-experienced patients were compared with placebo across the 3 triptan doses. The primary efficacy endpoint was headache response at 2 hours postdose. Secondary efficacy endpoints were 2-hour pain-free response, 2-hour absence of associated symptoms, 2-hour functional response, 24-hour sustained headache response, and 24-hour sustained pain-free response. RESULTS: For Eletriptan 20 mg, 40 mg, and 80 mg versus placebo, respectively, triptan-naive patients showed significantly higher 2-hour headache response (54%, 61%, 66% vs. 31%; P < .0001), 2-hour pain-free response (20%, 28%, and 31% vs. 8%; P < .0001), and 24-hour sustained headache response (34%, 45%, and 51% vs. 20%; P < .0001). A similarly significant efficacy advantage was also observed in the triptan-experienced subgroup for 2-hour headache response (46%, 63%, 69% vs. 21%; P < .0001), 2-hour pain-free response (13%, 32%, and 38% vs. 4%; P < .0001), and 24-hour sustained headache response (29%, 41%, and 45% vs. 9%; P < .0001). Previous treatment status did not influence tolerability, and all 3 doses of Eletriptan were well tolerated. CONCLUSIONS: These data suggest that Eletriptan has comparable efficacy versus placebo among both triptan-naive and triptan-experienced patients.

  • Eletriptan in migraine patients reporting unsatisfactory response to rizatriptan
    Headache, 2006
    Co-Authors: Jerome Goldstein, Kenneth S Albert, Paul T Tiseo, Chunming Li, Carolyn R Sikes
    Abstract:

    Objective.—The objective of this open-label study was to evaluate the efficacy of switching patients who had a previous unsatisfactory response to rizatriptan to Eletriptan 40 mg. Background.—The characteristics of individual migraine patients can vary tremendously and can have a significant impact on treatment outcomes. In addition, clinical experience has demonstrated that the triptans are not identical or interchangeable and that patients who respond poorly or who are dissatisfied with one agent can derive benefit by being switched to another agent within the triptan class. Methods.—Patients were eligible if they met International Headache Society criteria for migraine, with a frequency of 1 to 6 migraine attacks per month, and had documented “unsatisfactory treatment response” to rizatriptan within the past year (54% on the melt formulation; 46% on tablets). Reasons for dissatisfaction with rizatriptan (>1 could be cited) included inadequate (84%) or slow onset (50%) of pain relief, high recurrence rate (69%), and lack of improvement in associated symptoms (60%). One hundred twenty-three patients were eligible for treatment. Patients were instructed to take Eletriptan 40 mg as soon as they were certain that their headache was a migraine, regardless of level of pain severity (8% treated headaches that were mild). Results.—Headache response at 2 hours (first-attack data) was 64%. Absence of nausea (from baseline to 2 hours) increased from 50% to 78%, absence of photophobia from 30% to 72%, and absence of phonophobia from 39% to 77%. Functional response at 2 hours was 63%, with 41% of patients reporting normal functioning. Treatment with Eletriptan 40 mg was associated with a 27% to 40% reduction in migraine attack-related functional impairment, as measured by the PQ-7. Recurrence rates were 36.6%. Overall, 72% of patients rated Eletriptan as a “good-to-excellent” treatment, and 78% reported overall satisfaction with the degree of headache relief. Conclusion.—The results of this study suggest that Eletriptan is an efficacious treatment option for patients who are dissatisfied with their response to rizatriptan.

  • Eletriptan in the early treatment of acute migraine influence of pain intensity and time of dosing
    Cephalalgia, 2005
    Co-Authors: Jan Lewis Brandes, David Kudrow, Roger K Cady, P Tiseo, Carolyn R Sikes
    Abstract:

    This double-blind, placebo-controlled study was designed to evaluate the efficacy and tolerability of early treatment of a single migraine attack, when headache pain was mild, with two doses (20 mg and 40 mg) of Eletriptan. Patients (N = 613; female 79%; mean age 39 years) meeting International Headache Society criteria for migraine were encouraged, but not required, to utilize early treatment, thus providing an opportunity to assess the relative contribution to efficacy of pain severity and timing of dose. For the total patient sample (mild-to-severe headaches), 2-h pain-free rates were significantly higher than placebo (22%) on both Eletriptan 20 mg (35%; P < 0.01) and Eletriptan 40 mg (47%; P < 0.0001). For the cohort of patients who treated their headache when the pain intensity was mild, the 2-h pain-free rate on Eletriptan 40 mg was 68% compared with 25% on placebo (P < 0.0001). Pain intensity at the time of taking Eletriptan appeared to influence outcome more than the timing of the dose relative to...

Jayasena Hettiarachchi - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy of Eletriptan in Triptan‐Naïve Patients: Results of a Combined Analysis
    Headache, 2007
    Co-Authors: Vincent T Martin, Jayasena Hettiarachchi, Carolyn R Sikes, Mary Almas, Dominique Valade, Kenneth S Albert, Bruce Parsons
    Abstract:

    OBJECTIVE: To compare the efficacy and tolerability of Eletriptan 20 mg, 40 mg, and 80 mg in triptan-naive patients (who have not previously used triptans) versus triptan-experienced patients (who have previously used triptans). METHODS: Efficacy and tolerability data for Eletriptan 20 mg, 40 mg, and 80 mg were pooled from 10 similarly designed, randomized, parallel-group studies, and triptan-naive and triptan-experienced patients were compared with placebo across the 3 triptan doses. The primary efficacy endpoint was headache response at 2 hours postdose. Secondary efficacy endpoints were 2-hour pain-free response, 2-hour absence of associated symptoms, 2-hour functional response, 24-hour sustained headache response, and 24-hour sustained pain-free response. RESULTS: For Eletriptan 20 mg, 40 mg, and 80 mg versus placebo, respectively, triptan-naive patients showed significantly higher 2-hour headache response (54%, 61%, 66% vs. 31%; P < .0001), 2-hour pain-free response (20%, 28%, and 31% vs. 8%; P < .0001), and 24-hour sustained headache response (34%, 45%, and 51% vs. 20%; P < .0001). A similarly significant efficacy advantage was also observed in the triptan-experienced subgroup for 2-hour headache response (46%, 63%, 69% vs. 21%; P < .0001), 2-hour pain-free response (13%, 32%, and 38% vs. 4%; P < .0001), and 24-hour sustained headache response (29%, 41%, and 45% vs. 9%; P < .0001). Previous treatment status did not influence tolerability, and all 3 doses of Eletriptan were well tolerated. CONCLUSIONS: These data suggest that Eletriptan has comparable efficacy versus placebo among both triptan-naive and triptan-experienced patients.

  • efficacy of Eletriptan in triptan naive patients results of a combined analysis
    Headache, 2007
    Co-Authors: Vincent T Martin, Jayasena Hettiarachchi, Carolyn R Sikes, Mary Almas, Dominique Valade, Kenneth S Albert, Bruce Parsons
    Abstract:

    OBJECTIVE: To compare the efficacy and tolerability of Eletriptan 20 mg, 40 mg, and 80 mg in triptan-naive patients (who have not previously used triptans) versus triptan-experienced patients (who have previously used triptans). METHODS: Efficacy and tolerability data for Eletriptan 20 mg, 40 mg, and 80 mg were pooled from 10 similarly designed, randomized, parallel-group studies, and triptan-naive and triptan-experienced patients were compared with placebo across the 3 triptan doses. The primary efficacy endpoint was headache response at 2 hours postdose. Secondary efficacy endpoints were 2-hour pain-free response, 2-hour absence of associated symptoms, 2-hour functional response, 24-hour sustained headache response, and 24-hour sustained pain-free response. RESULTS: For Eletriptan 20 mg, 40 mg, and 80 mg versus placebo, respectively, triptan-naive patients showed significantly higher 2-hour headache response (54%, 61%, 66% vs. 31%; P < .0001), 2-hour pain-free response (20%, 28%, and 31% vs. 8%; P < .0001), and 24-hour sustained headache response (34%, 45%, and 51% vs. 20%; P < .0001). A similarly significant efficacy advantage was also observed in the triptan-experienced subgroup for 2-hour headache response (46%, 63%, 69% vs. 21%; P < .0001), 2-hour pain-free response (13%, 32%, and 38% vs. 4%; P < .0001), and 24-hour sustained headache response (29%, 41%, and 45% vs. 9%; P < .0001). Previous treatment status did not influence tolerability, and all 3 doses of Eletriptan were well tolerated. CONCLUSIONS: These data suggest that Eletriptan has comparable efficacy versus placebo among both triptan-naive and triptan-experienced patients.

  • patient preference for Eletriptan 80 mg versus subcutaneous sumatriptan 6 mg results of a crossover study in patients who have recently used subcutaneous sumatriptan
    European Journal of Neurology, 2005
    Co-Authors: Jean Schoenen, Carolyn R Sikes, Julio Pascual, S Rasmussen, Jayasena Hettiarachchi
    Abstract:

    : This current randomized, open-label, crossover study evaluated preference for oral Eletriptan 80 mg compared with subcutaneous sumatriptan 6 mg (suma-sc) amongst patients (n = 311) meeting IHS criteria for migraine who had recently used suma-sc, and found it well tolerated. Three attacks were treated on each study medication. Assessment of subjective preference was evaluated, after which patients freely chose which study medication they wished to use to treat each of three additional migraine attacks. A slight majority (50.6%) preferred or greatly preferred Eletriptan, whilst 43% preferred suma-sc. When permitted to choose between Eletriptan and suma-sc for subsequent treatment, 78% of patients who had preferred Eletriptan took Eletriptan during the extension phase for all three of their attacks, whilst only 37% of patients who preferred suma-sc took suma-sc for all of their extension-phase attacks (P < 0.05). Secondary efficacy measures showed comparable efficacy for each study medication, except for faster headache response and pain-free rates favor of suma-sc, and a significantly lower recurrence rate on Eletriptan (25% vs. 40%; P < 0.05). The results of this study suggest that Eletriptan is a strong alternative option for patients who have been prescribed suma-sc.

  • no effect of Eletriptan administration during the aura phase of migraine
    European Journal of Neurology, 2004
    Co-Authors: Jes Olesen, Jean Schoenen, H C Diener, Jayasena Hettiarachchi
    Abstract:

    : Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30-60 min before the headache phase starts. Administration of acute medication during aura should provide sufficient time to achieve therapeutic plasma levels, counteracting the headache. To test this hypothesis we evaluated the efficacy of Eletriptan 80 mg taken during aura. Patients met International Headache Society diagnostic criteria for migraine with aura, with an attack frequency of at least one per month and with aura occurring in > 50% of recent attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind, one attack, during the aura phase before headache, dose of either Eletriptan 80 mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean age, 40 years). The primary outcome measure was the proportion of patients not developing moderate-to-severe headache within 6 h post-dose. There was no significant difference in the proportion of patients developing moderate-to-severe headache on Eletriptan (61%) versus placebo (46%). Eletriptan was well tolerated and did not prolong the aura phase. Typical transient triptan adverse events were observed; most were mild-to-moderate in intensity. This study confirms the findings of two studies showing that triptans are ineffective but safe when given during the migraine aura phrase.

  • effectiveness of Eletriptan in acute migraine primary care for excedrin nonresponders
    Headache, 2004
    Co-Authors: Merle L Diamond, Jayasena Hettiarachchi, Barbara Hilliard, George H Sands, Robert Nett
    Abstract:

    Objective.—To evaluate the effectiveness of Eletriptan as a treatment for acute migraine in patients who were poor responders to Excedrin and had not yet been exposed to a triptan. Background.—Self-medication with over-the-counter drugs, such as Excedrin, is the most common treatment for migraine. Guidelines, however, recommend that triptans be used as first-line treatment of moderate to severe migraine—the severity affecting approximately 80% of migraineurs. Since over-the-counter medications, such as Excedrin, continue to be used in many patients, it is important that clinicians have information on the efficacy of triptans as first-line treatment and on treatment of migraineurs who have shown poor response to over-the-counter medications. Methods.—One hundred ten patients meeting criteria for migraine who were poor responders to Excedrin received open-label treatment with a 40-mg dose of Eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Results.—At 1 hour, the headache response rate was 44%; at 2 hours, 81%. The pain-free response rate at 1 hour was 14% and at 2 hours, 48%. At 2 hours, relief of baseline-associated symptoms ranged from 74% to 80%. Functional response was achieved by 82% of patients by 2 hours, and 68% of patients achieved relief of migraine that was sustained across 24 hours with no need for a second dose of Eletriptan or for rescue medication. Eletriptan was well tolerated with adverse events being transient and mild to moderate in intensity. Conclusion.—Previous studies have established the efficacy of Eletriptan as a first-line treatment for migraine. The results of this open-label trial demonstrate that the 40-mg dose of Eletriptan had a high degree of efficacy and tolerability among patients who were poor responders to Excedrin.

Aileen Mcharg - One of the best experts on this subject based on the ideXlab platform.

  • serotonergic effects and extracellular brain levels of Eletriptan zolmitriptan and sumatriptan in rat brain
    European Journal of Pharmacology, 2001
    Co-Authors: David E Johnson, Hans Rollema, Anne W Schmidt, Aileen Mcharg
    Abstract:

    Abstract In vivo microdialysis was used to assess the central serotonergic effects and extracellular brain levels of the 5-HT 1B/1D receptor agonists Eletriptan, zolmitriptan and sumatriptan in rats after intravenous and intracerebral administration, while their binding affinities and functional potencies were determined at 5-HT 1B , 5-HT 1D and 5-HT 1A receptors. In vitro studies showed that all three triptans are high affinity, full agonists at 5-HT 1B/1D receptors, but that sumatriptan is functionally less potent as a 5-HT 1B/1D agonist than zolmitriptan and Eletriptan. Local intracortical perfusion with the compounds via the dialysis probe decreased cortical 5-HT (5-hydroxytryptamine, serotonin) release with ED 50 values of approximately 0.1 μM for Eletriptan and zolmitriptan and 0.5 μM for sumatriptan. At 3.2 mg/kg i.v., both Eletriptan and zolmitriptan decreased 5-HT levels by about 35%, while sumatriptan had no effect, despite the fact that maximal sumatriptan concentrations in cortical dialysates were higher (8.8 nM at 20 min) than those of zolmitriptan (5.9 nM at 20 min) and Eletriptan (2.6 nM at 40 min). The observation that Eletriptan and zolmitriptan produce almost identical central serotonergic effects, after intracerebral as well as after systemic administration, is in agreement with their comparable functional 5-HT 1B/1D receptor agonist potencies and their free levels in cortical dialysates after 3.2 mg/kg i.v. On the other hand, the lack of central serotonergic effects of 3.2 mg/kg i.v. sumatriptan is likely due to its weaker functional 5-HT 1B/1D receptor agonist potency than Eletriptan and zolmitriptan, rather than lower brain levels, consistent with sumatriptan's fivefold lower potency after intracerebral administration.

  • The in vivo pharmacological profile of Eletriptan (UK-116,044): a potent and novel 5-HT1B/1D receptor agonist
    European Journal of Pharmacology, 2000
    Co-Authors: Paul Gupta, Paul Butler, Nick B Shepperson, Aileen Mcharg
    Abstract:

    The anti-migraine drug, Eletriptan [(R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl)ethyl]-1H-indole; UK-116,044], is a novel 5-HT1B/1D receptor agonist. In this paper, the regional vasoconstrictor profile of Eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibitory actions of Eletriptan on neurogenic inflammation in rat dura mater were also assessed. In the anaesthetised dog, Eletriptan (1–1000 μg kg−1 i.v.) produced a dose-dependent reduction of carotid arterial blood flow with a similar potency and maximum effect to sumatriptan (ED50 values: Eletriptan and sumatriptan, 12 and 9 μg kg−1, i.v., respectively). However, Eletriptan exhibited a significantly lower potency than sumatriptan in reducing coronary artery diameter (ED50 values: 63 and 19 μg kg−1, i.v., respectively, P

  • the in vivo pharmacological profile of Eletriptan uk 116 044 a potent and novel 5 ht1b 1d receptor agonist
    European Journal of Pharmacology, 2000
    Co-Authors: Paul Gupta, Paul Butler, Nick B Shepperson, Aileen Mcharg
    Abstract:

    The anti-migraine drug, Eletriptan [(R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl)ethyl]-1H-indole; UK-116,044], is a novel 5-HT1B/1D receptor agonist. In this paper, the regional vasoconstrictor profile of Eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibitory actions of Eletriptan on neurogenic inflammation in rat dura mater were also assessed. In the anaesthetised dog, Eletriptan (1–1000 μg kg−1 i.v.) produced a dose-dependent reduction of carotid arterial blood flow with a similar potency and maximum effect to sumatriptan (ED50 values: Eletriptan and sumatriptan, 12 and 9 μg kg−1, i.v., respectively). However, Eletriptan exhibited a significantly lower potency than sumatriptan in reducing coronary artery diameter (ED50 values: 63 and 19 μg kg−1, i.v., respectively, P<0.05). In the femoral circulation, sumatriptan caused a significant reduction in arterial blood flow (ED50 35 μg kg−1 i.v.) whereas Eletriptan (1–1000 μg kg−1 i.v.) had no significant effect upon femoral arterial blood flow when compared to vehicle-treated animals. In rats, Eletriptan (30–300 μg kg−1 i.v.) administered prior to electrical stimulation of the trigeminal ganglion produced a dose-related and complete inhibition of plasma protein extravasation in the dura mater (mean extravasation ratio: control 1.9; Eletriptan 1.0, minimum effective dose 100 μg kg−1, P<0.05). The potency and maximum effect of Eletriptan was identical to that of sumatriptan in this model. When administered during a period of continual stimulation of the trigeminal nerve, Eletriptan (100 μg kg−1 i.v.) produced a complete inhibition of plasma protein extravasation. The ability to reduce canine carotid arterial blood flow and inhibit neurogenic inflammation in rat dura mater suggests that vascular and neurogenic mechanisms may contribute to Eletriptan's clinical efficacy in migraine patients. In addition, Eletriptan exhibits some selectivity for reducing carotid arterial blood flow when compared with femoral arterial blood flow and coronary artery diameter, in the anaesthetised dog.

  • characterisation of the 5 ht receptor binding profile of Eletriptan and kinetics of 3h Eletriptan binding at human 5 ht1b and 5 ht1d receptors
    European Journal of Pharmacology, 1999
    Co-Authors: Carolyn Napier, Aileen Mcharg, M Stewart, H Melrose, B Hopkins, Rob Wallis
    Abstract:

    Abstract The affinity of Eletriptan (( R )-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl)ethyl]-1 H -indole) for a range of 5-HT receptors was compared to values obtained for other 5-HT 1B/1D receptor agonists known to be effective in the treatment of migraine. Eletriptan, like sumatriptan, zolmitriptan, naratriptan and rizatriptan had highest affinity for the human 5-HT 1B , 5-HT 1D and putative 5-ht 1f receptor. Kinetic studies comparing the binding of [ 3 H ] Eletriptan and [ 3 H ] sumatriptan to the human recombinant 5-HT 1B and 5-HT 1D receptors expressed in HeLa cells revealed that both radioligands bound with high specificity (>90%) and reached equilibrium within 10–15 min. However, [ 3 H ] Eletriptan had over 6-fold higher affinity than [ 3 H ] sumatriptan at the 5-HT 1D receptor ( K D : 0.92 and 6.58 nM, respectively) and over 3-fold higher affinity than [ 3 H ] sumatriptan at the 5-HT 1B receptor ( K D : 3.14 and 11.07 nM, respectively). Association and dissociation rates for both radioligands could only be accurately determined at the 5-HT 1D receptor and then only at 4°C. At this temperature, [ 3 H ] Eletriptan had a significantly ( P K on 0.249 min −1 nM −1 ) than [ 3 H ] sumatriptan ( K on 0.024 min −1 nM −1 ) and a significantly ( P K off 0.027 min −1 compared to 0.037 min −1 for [ 3 H ] sumatriptan). These data indicate that Eletriptan is a potent ligand at the human 5-HT 1B , 5-HT 1D and 5-ht 1f receptors and are consistent with its potent vasoconstrictor activity and use as a drug for the acute treatment of migraine headache.

  • characterisation of the contractile activity of Eletriptan at the canine vascular 5 ht1b receptor
    European Journal of Pharmacology, 1999
    Co-Authors: Paul Gupta, Jon Scatchard, Carolyn Napier, Aileen Mcharg, Rob Wallis
    Abstract:

    Abstract The functional activity of Eletriptan (( R )-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl)ethyl]-1 H -indole) at the contractile serotonin (5-hydroxytryptamine; 5-HT) `1B-like' receptor in dog isolated saphenous vein and basilar artery was investigated. Eletriptan, like 5-HT and sumatriptan potently contracted saphenous vein (pEC 50 : 6.3, 6.9 and 6.1, respectively) and basilar artery (pEC 50 7.2, 7.5 and 6.8, respectively). The maximum responses evoked by Eletriptan was, unlike sumatriptan, significantly lower than that to 5-HT (intrinsic activity saphenous vein: Eletriptan 0.57, 5-HT 1.0, sumatriptan 0.85; basilar artery: Eletriptan 0.77, 5-HT 0.98, sumatriptan 0.89). Contractions evoked by Eletriptan were antagonised by the 5-HT 1B/1D receptor antagonist GR125743 ( N -[4-methoxy-3-(4-methyl piperazin-1-yl)phenyl]-3-methyl-4-(4-pyridyl)benzamide) with p A 2 values of 9.1 in saphenous vein and 9.4 in basilar artery. Affinity estimates (p K A ) for 5-HT and sumatriptan determined from receptor alkylation studies in saphenous vein were 6.6 and 6.3, respectively, compared to the apparent equilibrium dissociation constant (p K P ) for Eletriptan of 6.8. The rank order of relative intrinsic efficacies ( e ) was 5-HT>sumatriptan>Eletriptan. Thus, Eletriptan required greater receptor occupancy (4.4-fold) to evoke an equivalent contraction to 5-HT and sumatriptan in dog isolated saphenous vein. These data demonstrate that Eletriptan is a potent partial agonist at the canine vascular 5-HT 1B receptor.

Elodie Ramos - One of the best experts on this subject based on the ideXlab platform.

  • a review of the pharmacoeconomics of Eletriptan for the acute treatment of migraine
    International Journal of General Medicine, 2015
    Co-Authors: Rahul Bhambri, Edward Schweizer, Jack Mardekian, Elodie Ramos
    Abstract:

    Migraine is a commonly occurring, chronic disorder that can cause significant disability. Eletriptan, a selective serotonin 5-hydroxytryptamine 1 receptor subtype B/D (5-HT1B/1D) agonist, is a clinically effective treatment for moderate to severe migraine. The objective of this literature review was to summarize the available data on the pharmacoeconomics of Eletriptan relative to other triptans. Articles meeting the following three criteria were included in the review: 1) contained pharmacoeconomic data on a marketed dose of Eletriptan; 2) included data on at least one other comparator triptan; and 3) was in English. A MEDLINE® search yielded a total of eight studies (from the European Union [n=5] and from the USA [n=3]) across multiple regions. Seven of the studies examined the pharmacoeconomics of Eletriptan relative to other triptans, and a further study examined the health care costs of Eletriptan 40 mg versus sumatriptan 100 mg. Eletriptan 40 mg was among a group of triptans, including rizatriptan 10 mg and almotriptan 12.5 mg, demonstrating the greatest cost-effectiveness. This result held across different definitions of efficacy (2 hours pain-free, sustained pain-free, and sustained pain-free with no adverse events) and also held when cost-effectiveness models accounted for second doses and use of rescue medication, management of adverse events, and productivity loss, in addition to drug acquisition costs. Only limited head-to-head comparator data were available. The majority of pharmacoeconomic studies utilized the same set of efficacy and/or tolerability data, and indirect costs were rarely included despite the fact that the majority of per capita migraine costs are attributable to indirect costs. In summary, although the market is now dominated by generics, Eletriptan 40 mg is among the most clinically and cost-effective oral triptans available for the management of acute migraine. Increased effectiveness/efficacy of Eletriptan may necessitate a lesser need for other migraine treatments and/or switching to other triptans.

  • outcome for headache and pain free nonresponders to treatment of the first attack a pooled post hoc analysis of four randomized trials of Eletriptan 40 mg
    Cephalalgia, 2014
    Co-Authors: Steve H Landy, Stewart J Tepper, Edward Schweizer, Mary Almas, Elodie Ramos
    Abstract:

    ObjectiveThe objective of this article is to evaluate, in first attack Eletriptan headache and pain-free nonresponders, the efficacy of treating a second and third attack with the same dose of Eletriptan 40 mg (ELE-40).MethodsData were pooled from four randomized, double-blind, placebo-controlled, multiple attack studies of Eletriptan in the treatment of migraine. The first-attack Eletriptan headache (HNR) and pain-free (PFNR) nonresponder samples consisted of patients who did not achieve headache or pain-free responses at two hours, or sustained headache or pain-free responses at 24 hours. The efficacy of the same dose of Eletriptan (vs placebo; PBO) in treating the second and third attacks was evaluated using a logistic regression model.ResultsAmong Attack 1 Eletriptan HNRs, treatment with ELE-40 (vs PBO) was associated with significantly higher two-hour headache response and pain-free rates, respectively, on both Attack 2 (48.8% vs 20.2%; 17.0% vs 3.9%; p < 0.0001 for both comparisons) and Attack 3 (37...

  • consistency of Eletriptan in treating migraine results of a randomized within patient multiple dose study
    Cephalalgia, 2014
    Co-Authors: Mary Almas, Stewart J Tepper, Edward Schweizer, Stephen H Landy, Elodie Ramos
    Abstract:

    ObjectiveThe current study evaluated the consistency of Eletriptan response.MethodsUsing a within-patient crossover design, patients with migraine completed a three-attack, open-label, lead-in period, before being treated, double-blind for four attacks, with either Eletriptan 40 mg (ELE-40; N = 539) or Eletriptan 80 mg (ELE-80; N = 432); placebo was randomly substituted for the treatment of one attack.ResultsOn an a priori analysis of within-patient consistency, double-blind treatment was associated with similar 2 hour headache response rates using a ≥2/3 response criterion for ELE-40 (77%) and ELE-80 (73%), and using a 3/3 response criterion for ELE-40 (46%) and ELE-80 (47%). Within-patient consistency in achieving pain-free status at 2 hours using a ≥2/3 criterion was slightly higher on ELE-40 (42%) compared with ELE-80 (38%), and was similar using the 3/3 criterion (18% on ELE-40, 17% on ELE-80). On a repeated measures logistic regression analysis across all treated attacks, the probability of achievin...

  • comparing the efficacy of Eletriptan for migraine in women during menstrual and non menstrual time periods a pooled analysis of randomized controlled trials
    Headache, 2014
    Co-Authors: Rahul Bhambri, Mary Almas, Vincent T Martin, Stephen D Silberstein, Younos Abdulsattar, Anjan Chatterjee, Elodie Ramos
    Abstract:

    Objective To assess the efficacy and tolerability of Eletriptan in treating migraine attacks occurring within the defined menstrual time period of 1 day before and 4 days after onset of menstruation (menses days –1 to +4) compared with attacks occurring during non-menstrual time periods (occurring outside of menses days –1 to +4). Background Migraine attacks during menses have been associated with longer duration, higher recurrence rates, greater treatment resistance, and greater functional disability than those not associated with menses. The efficacy of Eletriptan in treating migraine attacks associated with menstruation vs those outside a defined menstrual period has not been evaluated. Methods Data were pooled from 5 similarly designed, double-blind, randomized, placebo-controlled trials of Eletriptan 20 mg/40 mg/80 mg. Two groups were defined for this analysis: women with a single index migraine beginning during the menstrual (group 1) and non-menstrual (group 2) time periods. End points of interest were headache response at 2 hours, migraine recurrence and sustained responses for nausea, photo/phonophobia, and function. Logistic regression was used to compare group 1 vs group 2 and each Eletriptan dose (20, 40, or 80 mg) vs placebo. Adverse events were also assessed. Results Of 3217 subjects pooled from 5 studies, 2216 women were either in group 1 (n = 630) or group 2 (n = 1586). Rates of headache response at 2 hours were similar in group 1 vs group 2 (odds ratio [OR] = 1.11 [95% confidence interval (CI) 0.91, 1.36]; P = .2944). The rate of headache recurrence was significantly higher in group 1 vs group 2 (26.8% vs 18.6%; OR = 1.67 [95% CI 1.23, 2.26]; P < .001). The odds of achieving sustained nausea responses were significantly lower in group 1 than in group 2 (OR = 0.70 [95% CI 0.54, 0.92]; P = .0097). There was no significant difference between group 1 and group 2 in the odds of achieving a sustained photo/phonophobia and functional response (OR = 0.96 [95% CI 0.77, 1.20]; P = .7269 and OR = 1.14 [95% CI 0.87, 1.50]; P = .3425, respectively). Adverse events were comparable between group 1 and group 2. Conclusions Two-hour headache outcome measures were similar in women treated with Eletriptan both within and outside of the defined menstrual time period (menses days –1 to +4). The main treatment differences between the 2 groups occurred 2-24 hours post-treatment, with higher recurrence rates and lower sustained response rates for nausea in the group treated during the menstrual time period.

  • Comparing the Efficacy of Eletriptan for Migraine in Women During Menstrual and Non‐Menstrual Time Periods: A Pooled Analysis of Randomized Controlled Trials
    Headache, 2013
    Co-Authors: Rahul Bhambri, Mary Almas, Vincent T Martin, Stephen D Silberstein, Younos Abdulsattar, Anjan Chatterjee, Elodie Ramos
    Abstract:

    Objective To assess the efficacy and tolerability of Eletriptan in treating migraine attacks occurring within the defined menstrual time period of 1 day before and 4 days after onset of menstruation (menses days –1 to +4) compared with attacks occurring during non-menstrual time periods (occurring outside of menses days –1 to +4). Background Migraine attacks during menses have been associated with longer duration, higher recurrence rates, greater treatment resistance, and greater functional disability than those not associated with menses. The efficacy of Eletriptan in treating migraine attacks associated with menstruation vs those outside a defined menstrual period has not been evaluated. Methods Data were pooled from 5 similarly designed, double-blind, randomized, placebo-controlled trials of Eletriptan 20 mg/40 mg/80 mg. Two groups were defined for this analysis: women with a single index migraine beginning during the menstrual (group 1) and non-menstrual (group 2) time periods. End points of interest were headache response at 2 hours, migraine recurrence and sustained responses for nausea, photo/phonophobia, and function. Logistic regression was used to compare group 1 vs group 2 and each Eletriptan dose (20, 40, or 80 mg) vs placebo. Adverse events were also assessed. Results Of 3217 subjects pooled from 5 studies, 2216 women were either in group 1 (n = 630) or group 2 (n = 1586). Rates of headache response at 2 hours were similar in group 1 vs group 2 (odds ratio [OR] = 1.11 [95% confidence interval (CI) 0.91, 1.36]; P = .2944). The rate of headache recurrence was significantly higher in group 1 vs group 2 (26.8% vs 18.6%; OR = 1.67 [95% CI 1.23, 2.26]; P 

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  • comparative efficacy of Eletriptan and zolmitriptan in the acute treatment of migraine
    Cephalalgia, 2003
    Co-Authors: Timothy J Steiner, H C Diener, E A Macgregor, Jean Schoenen, Nancy Muirhead, Carolyn R Sikes
    Abstract:

    Eletriptan 40 mg and 80 mg have shown greater efficacy in acute migraine than oral sumatriptan 100 mg and naratriptan 2.5 mg. This study continues the systematic series of active comparator trials in the Eletriptan clinical development programme. In a multicentre double-blind, double-dummy, parallel-groups trial, 1587 outpatients with migraine by IHS criteria were randomised in a 3 : 3 : 3 : 1 ratio to Eletriptan 80 mg, Eletriptan 40 mg, zolmitriptan 2.5 mg or placebo. Of these, 1312 treated a single migraine attack and recorded baseline and outcome data to be included in the intention-to-treat population. The primary analysis was between Eletriptan 80 mg and zolmitriptan. For the primary efficacy end-point of 2-h headache response, rates were 74% on Eletriptan 80 mg, 64% on Eletriptan 40 mg, 60% on zolmitriptan (P < 0.0001 vs. Eletriptan 80 mg) and 22% on placebo (P < 0.0001 vs. all active treatments). Eletriptan 80 mg was superior to zolmitriptan on all secondary end-points at 1, 2 and 24 h, in most cas...

  • efficacy tolerability and safety of oral Eletriptan and ergotamine plus caffeine cafergot in the acute treatment of migraine a multicentre randomised double blind placebo controlled comparison
    Headache, 2003
    Co-Authors: Hanschristoph Diener, Julio Pascual, Janpeter Jansen, Avinoan Reches, Daniela Pitei, Timothy J Steiner
    Abstract:

    Eur Neurol. 2002;47(2):99-107 The 5-HT(1B/1D/1F) agonist Eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of Eletriptan and 2 tablets of Cafergot were compared in a double-blind, randomised, placebo-controlled, parallel-group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4-point scale (3  =  severe pain, 2  =  moderate pain, 1  =  mild pain, 0  =  no pain). Significantly more Eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated patients (33%; p  <  0.001) reported headache response (improvement from moderate-to-severe to mild or no pain) at 2 h. Substantially more Eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p  <  0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p  <  0.002 for each comparison). Both doses of Eletriptan were significantly more effective than Cafergot in reducing nausea (p  <  0.0001), photophobia (80 mg, p  <  0.0001; 40 mg, p  <  0.002), phonophobia (80 mg, p  <  0.0001; 40 mg, p  <  0.003) and functional impairment (p  <  or  =  0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral Eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated. Comment: As with all comparative trials with Eletriptan, this comparative trial raises the important issue of blinding. Was the Cafergot encapsulated (hence potentially hindering the early phase of absorbtion)? This approach has been a major issue with previous Eletriptan studies and may potentially make the results from this trial difficult to interpret. DSM One key issue in ensuring methodologically rigorous comparative trials is symmetry of comparative groups. I have come to believe that the controversy over encapsulation for blinding is neither about the pharmacokinetics of encapsulation, nor about the effectiveness of Eletriptan, but rather about the methodology of comparison, which requires as much symmetry as possible. As Gawel and Wiebe wrote in a superb article explaining how to critically evaluate a comparison trial, “When faced with a potential confounder … readers need to estimate in which direction the results would be biased” in any comparative trial (Gawel M, Wiebe S. Evidence-based analysis of a migraine treatment drug comparison trial. Cephalalgia. 2000;20[suppl 2]:33-38). SJT

  • Efficacy, tolerability and safety of oral Eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double‐blind, placebo‐controlled comparison.
    Headache, 2003
    Co-Authors: Hanschristoph Diener, Julio Pascual, Janpeter Jansen, Avinoan Reches, Daniela Pitei, Timothy J Steiner
    Abstract:

    Eur Neurol. 2002;47(2):99-107 The 5-HT(1B/1D/1F) agonist Eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of Eletriptan and 2 tablets of Cafergot were compared in a double-blind, randomised, placebo-controlled, parallel-group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4-point scale (3  =  severe pain, 2  =  moderate pain, 1  =  mild pain, 0  =  no pain). Significantly more Eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated patients (33%; p  

  • efficacy tolerability and safety of oral Eletriptan and ergotamine plus caffeine cafergot in the acute treatment of migraine a multicentre randomised double blind placebo controlled comparison
    European Neurology, 2002
    Co-Authors: Hanschristoph Diener, Julio Pascual, Janpeter Jansen, Avinoan Reches, Daniela Pitei, Timothy J Steiner
    Abstract:

    The 5-HT1B/1D/1F agonist Eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without

  • Effectiveness of Eletriptan in Reducing Time Loss Caused by Migraine Attacks
    PharmacoEconomics, 2000
    Co-Authors: Nicholas E J Wells, Timothy J Steiner
    Abstract:

    Background: The growing literature on the economics of migraine and its treatment generally indicates that the direct healthcare costs of managing the disorder are relatively low compared with the personal and societal burdens resulting from the disruption to normal functioning caused by migraine attacks. Objective: To investigate the effectiveness of Eletriptan, a new selective serotonin (5-hydroxytryptamine; 5-HT) 5-HTIB/IDagonist, in reducing both the patient-focused burden of migraine and the amount of work time foregone during a single attack. Design: In a phase III, multinational, randomised clinical trial, 692 patients treated a migraine attack with Eletriptan 40mg or 80mg, or placebo. Patients responded to a questionnaire seeking information concerning the amount of time lost from usual activities during the attack. Time loss assessments were made 24 hours after the last dose taken and recorded in a diary. Main outcome measures and results: Patients receiving either dose of the active compound were unable to perform their usual activities for a median period of 4 hours compared with 9 hours experienced by those taking placebo. This difference was highly statistically significant (p < 0.001). The time saving associated with Eletriptan usage reflected the differences in efficacy findings in the clinical component of the study. Conclusion: In this placebo-controlled trial, Eletriptan produced a significant reduction in the loss of usual functioning time associated with a migraine attack. This gain clearly represents a substantial benefit to patients with migraine irrespective of how it might most appropriately be valued in monetary terms. Further methodological progress in this area is warranted.