Sample records for naratriptan almotriptan frovatriptan
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Optimal balance of efficacy and tolerability of oral triptans and telcagepant
DEFF Research Database (Denmark)
Tfelt-Hansen, Peer
2011-01-01
Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant. The upper part of the efficacy curve of the triptans is generally flat, the so-called cei......Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant. The upper part of the efficacy curve of the triptans is generally flat, the so...
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Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine
Directory of Open Access Journals (Sweden)
Allais G
2016-10-01
Full Text Available Gianni Allais, Chiara Benedetto Department of Surgical Sciences, Women’s Headache Center, University of Turin, Turin, Italy Abstract: Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatriptan is a second-generation triptan with a longer terminal elimination half-life in blood than other triptans (~26 hours. Three double-blind, randomized crossover preference studies have been recently conducted, assessing efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan, respectively. Frovatriptan showed favorable tolerability and sustained effect, with a significantly lower rate of relapse over 48 hours versus the other triptans. These findings were confirmed in a series of analyses of patient subsets from the three studies, including patients with menstrually related and oral contraceptive-induced migraine, hypertension, obesity, weekend migraine, as well as patients with migraine with aura. In all patient subsets analyzed, lower headache recurrence rates were observed versus the comparator triptans, indicating a more sustained pain-relieving effect on migraine symptoms. A further randomized, double-blind study demonstrated that frovatriptan given in combination with the fast-acting cyclooxygenase inhibitor dexketoprofen provided improved migraine pain-free activity at 2 hours, and gave more sustained pain-free activity at 24 hours, versus frovatriptan alone. These benefits were observed both when the combination was administered early (<1 hour after symptom onset or late (>1 hour after onset. Different pharmacokinetic, but synergistic, properties between frovatriptan and dexketoprofen may make the combination of these agents particularly effective in migraine treatment, with rapid onset of action and sustained effect over 48 hours. These benefits, together with potential cost
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Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine
Allais, Gianni; Benedetto, Chiara
2016-01-01
Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatriptan is a second-generation triptan with a longer terminal elimination half-life in blood than other triptans (~26 hours). Three double-blind, randomized crossover preference studies have been recently conducted, assessing efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan, respectively. Frovatriptan showed favorable tolerability and sustained effect, with a significantly lower rate of relapse over 48 hours versus the other triptans. These findings were confirmed in a series of analyses of patient subsets from the three studies, including patients with menstrually related and oral contraceptive-induced migraine, hypertension, obesity, weekend migraine, as well as patients with migraine with aura. In all patient subsets analyzed, lower headache recurrence rates were observed versus the comparator triptans, indicating a more sustained pain-relieving effect on migraine symptoms. A further randomized, double-blind study demonstrated that frovatriptan given in combination with the fast-acting cyclooxygenase inhibitor dexketoprofen provided improved migraine pain-free activity at 2 hours, and gave more sustained pain-free activity at 24 hours, versus frovatriptan alone. These benefits were observed both when the combination was administered early (1 hour after onset). Different pharmacokinetic, but synergistic, properties between frovatriptan and dexketoprofen may make the combination of these agents particularly effective in migraine treatment, with rapid onset of action and sustained effect over 48 hours. These benefits, together with potential cost-effectiveness advantages versus other triptans could drive selection of the most appropriate treatment for acute migraine attacks. PMID:27757013
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Isolated naratriptan-associated ischemic colitis
Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven
2016-01-01
We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised. PMID:27695179
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Naratriptan in the Prophylactic Treatment of Cluster Headache.
Ito, Yasuo; Mitsufuji, Takashi; Asano, Yoshio; Shimazu, Tomokazu; Kato, Yuji; Tanahashi, Norio; Maruki, Yuichi; Sakai, Fumihiko; Yamamoto, Toshimasa; Araki, Nobuo
2017-10-01
Objective Naratriptan has been reported to reduce the frequency of cluster headache. The purpose of this study was to determine whether naratriptan is effective as a prophylactic treatment for cluster headache in Japan. Methods We retrospectively reviewed all 43 patients with cluster headache who received preventive treatment with naratriptan from April 2009 to April 2015. The International Classification of Headache Disorders, 3rd Edition (beta version) (ICHD-3 beta) was used to diagnose cluster headache. This study was conducted at 3 centers (Department of Neurology, Saitama Medical University; Saitama Neuropsychiatric Institute; Saitama Medical University International Medical Center). Patients were recruited from these specialized headache outpatient centers. Naratriptan was taken before the patient went to bed. Results The study population included 30 men (69.8%) and 13 women (30.2%). Twenty-two cases received other preventive treatments (51.2%), while 21 cases only received naratriptan (48.8%). Among the 43 cases, 37 patients (86.0%) achieved an improvement of cluster headache on naratriptan. Conclusion Naratriptan has been suggested as a preventive medicine for cluster headache because of the longer the biological half-life in comparison to other triptans. The internal use of naratriptan 2 hours before attacks appears to achieve a good response in patients with cluster headache.
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Managing migraine by patient profile: role of frovatriptan.
Cady, Roger K; Farmer, Kathleen
2016-01-01
For the last quarter of a century, triptans have been available for acute treatment of migraine but with little guidance on which of the different triptan products to use for which patient or which attack of migraine. In this article, we propose a structured approach to analysis of individual migraine attacks and patient characteristics as a means of defining and optimizing acute intervention. Assessment of patient and attack profiles includes the "5-Ps": pattern, phenotype, patient, pharmacology, and precipitants. Attending to these five components of information can assist in developing an individualized behavioral, pharmacological, and nonpharmacological comprehensive treatment plan for most migraine patients. This clinical approach is then focused on frovatriptan because of its unique molecular signature and potential novel clinical applications. Frovatriptan like all triptans is indicated for acute treatment of migraine but its role has been explored in management of several unique migraine phenotypes. Frovatriptan has the longest half-life of any triptan and consequently is often promoted for acute treatment of migraine of longer duration. It has also been studied as a short-term preventive treatment in women with menstrual-related migraine. Given that 60% of female migraineurs suffer from menstrual-related migraine, this population is the obvious group for continued study. Small studies have also explored frovatriptan's use in treating migraine predicted by premonitory symptoms as a preventive for the headache phase of migraine. By identifying patient and attack profiles, clinicians may effectively determine the viability of frovatriptan as an effective pharmacological intervention for migraine.
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Naratriptan hydrochloride in extemporaneosly compounded oral suspensions.
Zhang, Y P; Trissel, L A; Fox, J L
2000-01-01
The purpose of this study was to determine the pharmaceutical acceptability and chemical stability of naratriptan hydrochloride in three extemporaneously compounded suspension formulations. The naratriptan-hydrochloride oral suspensions were prepared from 2.5-mg commercial tablets yielding a nominal naratriptan concentration of 0.5 mg/mL. The suspension vehicles selected for testing were Syrpalta, an equal-parts mixture of Ora-Plus and Ora-Sweet, and an equal-parts mixture of Ora-Plus and Ora-Sweet SF. The tablets were crushed and thoroughly triturated to a fine powder using a porcelain mortar and pestle. The powder was incorporated into a portion of the Syrpalta or Ora-Plus suspension vehicle and mixed until homogeneous. The mixtures were then brought to volume with Syrpalta, Ora-Sweet or Ora-Sweet SF, as appropriate. The suspensions were packaged in amber, plastic, screw-cap prescription bottles and stored at 23 deg C for seven days and 4 deg C for 90 days. An adequate suspension was never achieved in Syrpalta. The crushed-tablet powder did not produce a uniformly dispersed mixture and exhibited clumping and a high rate of sedimentation. A distinct layer of the solid tablet material settled immediately after shaking. Over the next four hours, a densely packed, yellow, caked layer formed at the bottom of the containers, making resuspension difficult. During storage, the caking became worse. Chemical analysis was not performed. The Ora-Plus and Ora-Sweet or Ora-Sweet SF suspensions had a slight greenish cast and were resuspended without difficulty by shaking for approximately ten seconds, yielding easily poured and homogeneous mixtures throughout the study. Visible settling and layering did not begin for four hours with the Ora-Sweet suspension and 24 hours for the Ora-Sweet SF suspension. High pressure liquid chromatographic analysis found that the naratriptan concentration in both suspension-vehicle combinations exhibited little or no loss for seven days at 23
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Managing migraine by patient profile: role of frovatriptan
Directory of Open Access Journals (Sweden)
Cady RK
2016-04-01
Full Text Available Roger K Cady, Kathleen Farmer Headache Care Center, Springfield, MO, USA Abstract: For the last quarter of a century, triptans have been available for acute treatment of migraine but with little guidance on which of the different triptan products to use for which patient or which attack of migraine. In this article, we propose a structured approach to analysis of individual migraine attacks and patient characteristics as a means of defining and optimizing acute intervention. Assessment of patient and attack profiles includes the “5-Ps”: pattern, phenotype, patient, pharmacology, and precipitants. Attending to these five components of information can assist in developing an individualized behavioral, pharmacological, and nonpharmacological comprehensive treatment plan for most migraine patients. This clinical approach is then focused on frovatriptan because of its unique molecular signature and potential novel clinical applications. Frovatriptan like all triptans is indicated for acute treatment of migraine but its role has been explored in management of several unique migraine phenotypes. Frovatriptan has the longest half-life of any triptan and consequently is often promoted for acute treatment of migraine of longer duration. It has also been studied as a short-term preventive treatment in women with menstrual-related migraine. Given that 60% of female migraineurs suffer from menstrual-related migraine, this population is the obvious group for continued study. Small studies have also explored frovatriptan’s use in treating migraine predicted by premonitory symptoms as a preventive for the headache phase of migraine. By identifying patient and attack profiles, clinicians may effectively determine the viability of frovatriptan as an effective pharmacological intervention for migraine. Keywords: frovatriptan, acute treatment, preventive therapy, early intervention
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DEFF Research Database (Denmark)
Tfelt-Hansen, Peer Carsten
2011-01-01
Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs are publi......Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs...... are published in full. Naratriptan 2.5 mg is superior to placebo for acute migraine treatment in 6 RCTs, but inferior to sumatriptan 100 mg and rizatriptan 10 mg in one RCT each. This dose of naratriptan has no more adverse events than placebo. Naratriptan 1 mg b.i.d. has some effect in the short...
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Sublingual Delivery of Frovatriptan: An Indication of Potential Alternative Route
Verma, Surajpal; Prasad, Shyam Baboo
2014-01-01
Frovatriptan, a 5-HT1B and 5-HT1D receptor agonist, is used for the treatment of acute migraine attack. This molecule is classified into second line therapy because of its slow onset of action (peak response obtained after 4 hours of administration) and low bioavailability (25%). Moreover, its therapy is the most costly among all triptans. Attempt has been made in present work to suggest a way out to fasten its onset of action and to enhance its bioavailability. Prepared tablets were evaluated by physicochemical tests, in vitro permeation studies, ex vivo permeation studies, and histopathological studies. Suitable mathematical calculations were performed to calculate the minimum amount of bioavailability that could be enhanced. Tablets containing chitosan (5% w/w) were found to give optimum results. Prepared tablets can double the bioavailability of frovatriptan and can initiate its response within 10 minutes of its administration. Suggestive alternative has the potential to increase the efficacy of frovatriptan for treating acute migraine attack. PMID:27433492
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Hernández, Carla Navarro; Martín-Yerga, Daniel; González-García, María Begoña; Hernández-Santos, David; Fanjul-Bolado, Pablo
2018-02-01
Naratriptan, active pharmaceutical ingredient with antimigraine activity was electrochemically detected in untreated screen-printed carbon electrodes (SPCEs). Cyclic voltammetry and differential pulse voltammetry were used to carry out quantitative analysis of this molecule (in a Britton-Robinson buffer solution at pH 3.0) through its irreversible oxidation (diffusion controlled) at a potential of +0.75V (vs. Ag pseudoreference electrode). Naratriptan oxidation product is an indole based dimer with a yellowish colour (maximum absorption at 320nm) so UV-VIS spectroelectrochemistry technique was used for the very first time as an in situ characterization and quantification technique for this molecule. A reflection configuration approach allowed its measurement over the untreated carbon based electrode. Finally, time resolved Raman Spectroelectrochemistry is used as a powerful technique to carry out qualitative and quantitative analysis of Naratriptan. Electrochemically treated silver screen-printed electrodes are shown as easy to use and cost-effective SERS substrates for the analysis of Naratriptan. Copyright © 2017 Elsevier B.V. All rights reserved.
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Creatin-kinase elevation after accidental ingestion of almotriptan in an 18-month-old girl.
Castagno, E; Lupica, M; Viola, S; Savino, F; Miniero, R
2014-02-01
Few studies have been published to demonstrate tolerability and efficacy of almotriptan in adolescents and children with migraine, particularly in the first years of life, though preliminary results are favorable. We report the case of an 18-month-old infant with elevation of serum levels of creatin-kinase after the accidental ingestion of almotriptan. A previously healthy 18-month-old girl (weight: 13 kg) was admitted to our Department four hours after the accidental ingestion of 6.25 mg of almotriptan (0.48 mg/kg), without any specific symptom. The performed investigations showed high serum levels of creatin-kinase (CK) (527 IU/L; normal values: 24-170 IU/L). Transaminase, creatinine, aldolase, myoglobin and troponin T serum levels were normal. The electrocardiogram proved negative. Initial management consisted of parenteral rehydration with saline solution. CK levels lowered significantly at 12 hours (455 IU/L) and at 65 hours (188 IU/L) after the ingestion. No symptoms were observed before discharge and on follow-up.
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Tullo, Vincenzo; Valguarnera, Fabio; Barbanti, Piero; Cortelli, Pietro; Sette, Giuliano; Allais, Gianni; d'Onofrio, Florindo; Curone, Marcella; Zava, Dario; Pezzola, Deborha; Benedetto, Chiara; Frediani, Fabio; Bussone, Gennaro
2014-05-01
Drugs for migraine attacks include triptans and NSAIDs; their combination could provide greater symptom relief. A total of 314 subjects with history of migraine, with or without aura, were randomized to frovatriptan 2.5 mg alone (Frova), frovatriptan 2.5 mg + dexketoprofen 25 mg (FroDex25) or frovatriptan 2.5 mg + dexketoprofen 37.5 mg (FroDex37.5) and treated at least one migraine attack. This was a multicenter, randomized, double-blind, parallel-group study. The primary end point was the proportion of pain free (PF) at two hours. Secondary end points were PF at one and four hours, pain relief (PR) at one, two, four hours, sustained PF (SPF) at 24 and 48 hours, recurrence at 48 hours, resolution of nausea, photophobia and phonophobia at two and four hours, the use of rescue medication and the judgment of the treatment. The results were assessed in the full analysis set (FAS) population, which included all subjects randomized and treated for whom at least one post-dose intensity of headache was recorded. The proportions of subjects PF at two hours (primary end point) were 29% (27/93) with Frova compared with 51% (48/95 FroDex25 and 46/91 FroDex37.5) with each combination therapies ( P dexketoprofen. FroDex improved initial efficacy at two hours compared to Frova whilst maintaining efficacy at 48 hours in this study. Tolerability profiles were comparable. Intrinsic pharmacokinetic properties of the two single drugs contribute to this improved efficacy profile.
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Allais, Gianni; Rolando, Sara; De Lorenzo, Cristina; Benedetto, Chiara
2014-08-01
Frovatriptan is a triptan characterized by a high affinity for 5-HT1B/1D receptors and a long half-life contributing to a more sustained and prolonged action than other triptans. Dexketoprofen is a nonsteroidal anti-inflammatory drug with a relatively short half-life and rapid onset of action, blocking the action of cyclo-oxygenase, which is involved in prostaglandins' production, thus reducing inflammation and pain. Both drugs have been successfully employed as monotherapies for the treatment of acute migraine attacks. The combination of these two drugs (frovatriptan 2.5 mg plus dexketoprofen 25 or 37.5 mg) has been tested in migraine sufferers, showing a rapid and good initial efficacy, with 2-h pain free rates of 51%, and a high persistence in the 48-h following the onset of pain: recurrence occurred in only 29% of attacks and sustained pain free rates were 43% at 24- and 33% at 48-h.
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Stange, Ulrike; Führling, Christian; Gieseler, Henning
2014-04-01
The purpose of this study was to develop and manufacture novel freeze-dried orally disintegrating tablets (ODTs) for migraine therapy containing taste-masked naproxen sodium and naratriptan hydrochloride. The formulation was optimized based on freeze-drying of sucrose solutions with different binders (hydroxyethylstarch, sodium alginate, methylcellulose, and gelatin) and varying amounts of Eudragit® E-coated naproxen sodium granules. Excellent product performance of the ODTs in terms of hardness and disintegration time (hydrochloride, and taste-masked naproxen sodium granules corresponding to 200 mg of naproxen were then added, and the final batches of ODTs for migraine therapy were produced. The ODTs were fully characterized, and subsequently stored for 1 month at room temperature and at 40°C. The amount of free naproxen sodium after freeze-drying and storage was below the threshold bitterness value, and the coating remained intact. Additionally, the particle size distribution of taste-masked granules was preserved, and more than 90 % naproxen sodium was released after 30 min. Naratriptan hydrochloride was dissolved immediately after disintegration, hence facilitating buccal absorption of the active pharmaceutical ingredient. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
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Allais, G; Bussone, G; Tullo, V; Cortelli, P; Valguarnera, F; Barbanti, P; Sette, G; D'Onofrio, F; Curone, M; Benedetto, C
2015-01-01
The purpose of this article is to investigate the efficacy and safety of frovatriptan plus dexketoprofen 25 or 37.5 mg (FroDex25 or FroDex37.5, respectively) compared to that of frovatriptan 2.5 mg (Frova) in menstrually related migraine (MRM). The aim of this article is to analyze a subgroup of 76 women who treated an MRM attack in this multicenter, randomized, double-blind, parallel-group study. The primary end-point was the proportion of patients who were pain free (PF) at two hours. Secondary end-points included pain-relief (PR) at two hours and 48 hours sustained pain free (SPF). PF rates at two hours were 29% under Frova, 48% under FroDex25 and 64% under FroDex37.5 (p dexketoprofen produced higher PF rates at two hours compared to Frova while maintaining efficacy at 48 hours. Tolerability profiles were comparable. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
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Calışkan, Necla; Sögüt, Eda; Saka, Cafer; Yardım, Yavuz; Sentürk, Zuhre
2010-09-01
This paper is the first report describing the characterization of local diatomite of Caldiran-Van region (Eastern Anatolia, Turkey). Special attention was paid to the ability of its electroanalytical performance at modified electrodes and to the potential application of diatomite-modified electrode. For this purpose, the determination of Naratriptan which is a novel oral triptan (5-hydroxytryptamine receptor agonist) in migraine treatment, by means of a carbon paste electrode modified with 10% (w/w) of diatomite was studied using cyclic and square-wave voltammetry. The experimental conditions that affect the electrode reaction process were studied in terms of pH of the supporting electrolyte, scan rate, accumulation variables, modifier composition and square-wave parameters. Using square-wave stripping mode, the drug yielded a well-defined voltammetric response in Britton-Robinson buffer, pH 4.0 at 0.84 V (vs. Ag/AgCl) (a pre-concentration step being carried out with an open circuit at 120 s). The process could be used to determine Naratriptan concentrations in the range 5x10(-7)-9x10(-7) M, with a detection limit of 1.25x10(-7) M (46.5 mug L(-1)). The applicability of the method to spiked human urine samples was illustrated.
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Oral transmucosal delivery of naratriptan.
Sattar, Mohammed; Lane, Majella E
2016-11-30
Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.
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Bussone, G; Tullo, V; Cortelli, P; Valguarnera, F; Barbanti, P; Sette, G; D’Onofrio, F; Curone, M; Benedetto, C
2015-01-01
Purpose The purpose of this article is to investigate the efficacy and safety of frovatriptan plus dexketoprofen 25 or 37.5 mg (FroDex25 or FroDex37.5, respectively) compared to that of frovatriptan 2.5 mg (Frova) in menstrually related migraine (MRM). Aim The aim of this article is to analyze a subgroup of 76 women who treated an MRM attack in this multicenter, randomized, double-blind, parallel-group study. Methods The primary end-point was the proportion of patients who were pain free (PF) at two hours. Secondary end-points included pain-relief (PR) at two hours and 48 hours sustained pain free (SPF). Results PF rates at two hours were 29% under Frova, 48% under FroDex25 and 64% under FroDex37.5 (p dexketoprofen produced higher PF rates at two hours compared to Frova while maintaining efficacy at 48 hours. Tolerability profiles were comparable. PMID:25053749
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High Performance Liquid Chromatographic Analysis of Almotriptan Malate in Bulk and Tablets
Directory of Open Access Journals (Sweden)
Chandra Bala Sekaran
2013-02-01
Full Text Available Purpose: A simple RP-HPLC method has been developed and validated for the determination of almotriptan malate (ATM in bulk and tablets. Methods: Chromatographic separation of ATM was achieved by using a Thermo Scientific C18 column. A Mobile phase containing a mixture of methanol, water and acetic acid (4:8:0.1 v/v was pumped at the flow rate of 1 mL/min. Detection was performed at 227 nm. According to ICH guidelines, the method was validated. Results: The calibration curve was linear in the concentration range 5–60 μg/mL for the ATM with regression coefficient 0.9999. The method was precise with RSD <1.2%. Excellent recoveries of 99.60 - 100.80% proved the accuracy of the method. The limits of detection and quantification were found to be 0.025 and 0.075 μg/mL, respectively. Conclusion: The method was successfully applied for the quantification of ATM in tablets with acceptable accuracy and precision.
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Clinical aspects of perimenstrual headaches.
Taylor, Frederick R
2009-02-01
Menstrual migraine (MM) is either pure, if attacks are limited solely during the perimenstrual window (PMW), or menstrually related (MRM), if two of three PMWs are associated with attacks with additional migraine events outside the PMW. Acute migraine specific therapy is equally effective in MM and non-MM. Although the International Classification of Headache Disorders-II classifies MM without aura, data suggest this needs revision. The studies on extended-cycle oral contraceptives suggest benefits for headache-prone individuals. Triptan mini-prophylaxis outcomes are positive, but a conclusion of "minimal net benefit compared to placebo" is not entirely unwarranted. In a 2008 evidence-based review, grade B recommendations exist for sumatriptan (50 and 100 mg), mefenamic acid (500 mg), and riza-triptan (10 mg) for the acute treatment of MRM. For the preventive mini-prophylactic treatment of MRM, grade B recommendations are provided for transcutaneous estrogen (1.5 mg), frovatriptan (2.5 mg twice daily), and naratriptan (1 mg twice daily).
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Allais, Gianni; Bussone, Gennaro; Tullo, Vincenzo; Cortelli, Pietro; Valguarnera, Fabio; Barbanti, Piero; Sette, Giuliano; Frediani, Fabio; D'Arrigo, Giacomo; d'Onofrio, Florindo; Comi, Giancarlo; Curone, Marcella; Colombo, Bruno; Omboni, Stefano; Benedetto, Chiara
2015-05-01
The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.
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Directory of Open Access Journals (Sweden)
Balasekhara Reddy Challa
2011-03-01
Full Text Available The authors developed a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS method for the quantification of naratriptan (NP in human plasma using naratriptan-d3 (NPD3 as an internal standard (IS. Chromatographic separation was performed on a Zorbax SB-C18, 75 x 4.6 mm, 3.5 µm column with an isocratic mobile phase composed of 0.1% formic acid : acetonitrile (50:50 v/v, at a flow-rate of 0.6 mL/min. NP and NPD3 were detected with proton adducts at m/z 336.5→98.0 and 339.4→101.0 in selected reaction monitoring (SRM positive mode, respectively. The liquid-liquid extraction method was used to extract the NP and NPD3. This method was validated over a linear concentration range of 0.1-25.0 ng/mL with a correlation coefficient of (r2 > 0.9998. The Intra-day and Interday precision was found to be 1.8 to 3.6%, and 2.3 to 2.6%, and accuracy to be 101.7- 104.2% and 101.8 to 102.9%, respectively. NP was found to be stable throughout freeze-thaw (three cycles, bench top and auto sampler stability studies. This method was successfully applied for the analysis of plasma samples following oral administration of NP (2.5 mg in 31 healthy Indian male human volunteers under fasting conditions.Os autores desenvolveram um método simples, sensível e específico de cromatografia líquida-espectrometria de massa-tandem (LC-MS/MS para a quantificação de naratriptan (NP em plasma humano empregando naratriptan-d3 (NPD3 como padrão interno de referência (IS. A separação cromatográfica foi realizada em coluna Zorbax SB-C18, 75 x 4,6 mm, 3,5 μm com fase móvel isocrática composta por 0,1% ácido fórmico : acetronitrila (50:50 v/v e taxa de fluxo de 0,6 mL/min. NP e NPD3 foram detectados com adutos de prótons a m/z 336.5→98.0 e 339.4→101.0 in em modo positivo do tipo monitoramento de reação selecionada (SRM, respectivamente. Extração líquido-líquido foi empregada para extrair NP e NPD3, sendo o método validado
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Triptans and migraine: advances in use, administration, formulation, and development.
Macone, Amanda E; Perloff, Michael D
2017-03-01
Recent triptan development has focused on new administration methods and formulations, triptan combination therapies, treatment in menstrually related migraines, and novel serotonin receptor subtype agonists (5HTf). Areas covered: Clinical triptan research related to migraine was reviewed, analyzing EMBASE and PUBMED data bases from 01/01/2011 to 06/29/2016, with a focus on clinical trials of class 1 or 2 level of evidence. There have been advances in drug combination therapies, as well as administration devices that aid in ease of use, increase efficacy, and decrease adverse reactions. Some new agents and devices have similar or less efficacy compared to previous generic triptan formulations. New agents have action at the 5HTf receptor subtype, and avoid vascular side effects of classic 5Ht1b/d agonists, however adverse reactions may limit their clinic use. Long half-life triptans, frovatriptan and naratriptan, do appear to have good benefit in menstral related migraine. Expert opinion: Recent advances in triptan development can offer some advantages to migraine therapy and patient preferences, but have a much higher cost compared to individual generic triptan agents. In the coming years, triptan advances with high efficacy, limiting ADRs and cost are welcomed, in this regard the 5HT1b/d triptans are already well established.
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Saibaba, B; Vishnuvardhan, Ch; Johnsi Rani, P; Satheesh Kumar, N
2018-01-01
Almotriptan maleate (ALMT), a highly selective 5-hydroxy tryptamine 1B/1D (5-HT1B/1D) receptor agonist used in the treatment of migraine headache was subjected to various ICH (Q1A (R2)) specified guidelines. The drug underwent significant degradation under hydrolytic (acid, base and neutral), oxidative and photolytic stress conditions, while it was stable under thermal stress condition. A total of seven significant degradation products (DPs) were obtained. A simple, selective and reliable UPLC method has been developed for the separation of ALMT and its DPs using Acquity UPLC HSS Cyano (100 × 2.1 mm, 1.8 μm) column with mobile phase consisting of ammonium acetate (10 mM, pH 4.4) buffer and acetonitrile in gradient elution mode. Chromatographic analysis was performed at a flow rate of 0.3 mL/min using a PDA detector at a wavelength of 230 nm. All the DPs (DP-1 to DP-7) were characterized using UHPLC-ESI-QTOF based on mass fragmentation pattern and accurate m/z values. The developed UPLC method was validated in terms of specificity, linearity, precision and accuracy. The developed stability-indicating method helps in quantification of drug in the presence of DPs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Comparative tolerability of treatments for acute migraine: A network meta-analysis.
Thorlund, Kristian; Toor, Kabirraaj; Wu, Ping; Chan, Keith; Druyts, Eric; Ramos, Elodie; Bhambri, Rahul; Donnet, Anne; Stark, Richard; Goadsby, Peter J
2017-09-01
Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified. Methods We performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting. Results Our search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all
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... signals from being sent to the brain, and blocking the release of certain natural substances that cause ... or get emergency medical treatment: swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or ...
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... works by narrowing blood vessels around the brain, blocking pain signals from being sent to the brain, ... in the hands or feet swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or ...
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Orlandini, S; Pasquini, B; Stocchero, M; Pinzauti, S; Furlanetto, S
2014-04-25
The development of a capillary electrophoresis (CE) method for the assay of almotriptan (ALM) and its main impurities using an integrated Quality by Design and mixture-process variable (MPV) approach is described. A scouting phase was initially carried out by evaluating different CE operative modes, including the addition of pseudostationary phases and additives to the background electrolyte, in order to approach the analytical target profile. This step made it possible to select normal polarity microemulsion electrokinetic chromatography (MEEKC) as operative mode, which allowed a good selectivity to be achieved in a low analysis time. On the basis of a general Ishikawa diagram for MEEKC methods, a screening asymmetric matrix was applied in order to screen the effects of the process variables (PVs) voltage, temperature, buffer concentration and buffer pH, on critical quality attributes (CQAs), represented by critical separation values and analysis time. A response surface study was then carried out considering all the critical process parameters, including both the PVs and the mixture components (MCs) of the microemulsion (borate buffer, n-heptane as oil, sodium dodecyl sulphate/n-butanol as surfactant/cosurfactant). The values of PVs and MCs were simultaneously changed in a MPV study, making it possible to find significant interaction effects. The design space (DS) was defined as the multidimensional combination of PVs and MCs where the probability for the different considered CQAs to be acceptable was higher than a quality level π=90%. DS was identified by risk of failure maps, which were drawn on the basis of Monte-Carlo simulations, and verification points spanning the design space were tested. Robustness testing of the method, performed by a D-optimal design, and system suitability criteria allowed a control strategy to be designed. The optimized method was validated following ICH Guideline Q2(R1) and was applied to a real sample of ALM coated tablets
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Acute migraine therapy: recent evidence from randomized comparative trials
DEFF Research Database (Denmark)
Mett, A.; Tfelt-Hansen, P.
2008-01-01
(1) A wide array of data regarding acute migraine treatment are available, but few trials strictly adhere to International Headache Society guidelines for patient inclusion criteria. (2) Triptans appear to have similar efficacy profiles, but among newer triptans, almotriptan offers improved...
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Tsaltas, Eleftheria; Kontis, Dimitris; Chrysikakou, Sofia; Giannou, Haralambos; Biba, Angeliki; Pallidi, Stella; Christodoulou, Angeliki; Maillis, Antonis; Rabavilas, Andreas
2005-05-15
This study introduces a laboratory model of compulsive behavior based on persistence in the context of rewarded spatial alternation. Rats were screened for spontaneous persistence during T-maze reinforced alternation. Experiment 1: One high and one low spontaneous persistence group (n = 8) received 20 injections of fluoxetine, a matched pair saline, both followed by 4 days of meta-chlorophenylpiperazine (mCPP) challenge. Experiment 2: Five matched groups of rats (n = 9) received pretreatment (20 injections) with fluoxetine, mCPP, desipramine, diazepam or saline, followed by 4 days of mCPP challenge (fluoxetine in mCPP group). After washout, animals received 2 days of naratriptan, followed by another 2-day mCPP challenge. In both experiments mCPP significantly increased persistence in saline controls. Fluoxetine also acutely increased persistence scores: after a gradual return to baseline, these scores showed tolerance to mCPP. Experiment 1: This pattern was significant in high but not low initial persistence groups. Experiment 2: Fluoxetine and mCPP showed cross-tolerance. Neither desipramine nor diazepam protected against mCPP challenge. Persistence scores returned to baseline during washout and naratriptan and were thereafter increased by another mCPP challenge in all but the fluoxetine and mCPP groups, suggesting 5-HT2C receptor mediation. This model is based on spontaneous persistence behavior showing pharmacological responses concordant with those of compulsive symptomatology.
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Ptácek, Pavel; Klíma, Josef; Macek, Jan
2009-03-15
A high-performance liquid chromatographic method with fluorescence detection for the determination of itopride in human plasma is reported. The sample preparation was based on liquid-liquid extraction of itopride from plasma with t-butylmethylether and dichloromethane (70:30, v/v) mixture followed by a back extraction of the analyte to the phosphate buffer (pH 3.2). Liquid chromatography was performed on an octadecylsilica column (55 mm x 4 mm, 3 microm particles), the mobile phase consisted of acetonitrile-triethylamine-15 mM dihydrogenpotassium phosphate (14.5:0.5:85, v/v/v), pH of the mobile phase was adjusted to 4.8. The run time was 3 min. The fluorimetric detector was operated at 250/342 nm (excitation/emission wavelength). Naratriptan was used as the internal standard. The limit of quantitation was 9.5 ng/ml using 0.5 ml of plasma. The method precision and inaccuracy were less than 8%. The assay was applied to the analysis of samples from a bioequivalence study.
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Tomillero, A; Moral, M A
2010-01-01
(-)-Epigallocatechin gallate, Abafungin, ACE-031, Adapalene/benzoyl peroxide, AE-37, Aflibercept, AGS-003, Albiglutide, Alemtuzumab, Aliskiren fumarate, ALT-801, AN-2728, Anacetrapib, API, Aprepitant, ARQ-197, Ascorbic acid, Atazanavir sulfate, ATN-224, AVI-4658, Azacitidine, Azelnidipine; Belinostat, Bevacizumab, BI-2536, Biphasic insulin aspart, Bortezomib, Bovine lactoferrin, Bryostatin 1, Budesonide/formoterol fumarate; cAC10, Canfosfamide hydrochloride, Cediranib, Clofarabine, Cocaine conjugate vaccine; Darbepoetin alfa, Dasatinib, Denosumab, Disomotide, Doripenem, Dovitinib Lactate, Dronedarone hydrochloride, Drospirenone/estradiol, Dutasteride; Ecogramostim, Entinostat, Enzastaurin hydrochloride, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fampridine, Fenretinide LXS, FFR-factor VIIa, Fingolimod hydrochloride, Frovatriptan; Gefitinib, Gimatecan, GP-2/GM-CSF; Iloperidone, Imatinib mesylate, Indibulin, Ipilimumab, Ivabradine hydrochloride; Lactobacillus rhamnosus, Lapatinib ditosylate, LC-07, Lenalidomide, Linifanib, Liposomal doxorubicin, Liposomal vincristine, Litenimod, Lutein; M-118, MDX-1401, MEDI-528, Midostaurin, Miglustat, MK-0657; Natalizumab, Nesiritide, NGR-TNF, Niacin/simvastatin; Obatoclax mesylate, Olaparib, Omacetaxine mepesuccinate; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Palonosetron hydrochloride, Pazopanib hydrochloride, Pegfilgrastim, Pemetrexed disodium, PER.C-flu, Perifosine, PF-02341066, Pimecrolimus, Pitrakinra, Plerixafor hydrochloride, Posaconazole; Rasburicase, Recombinant human relaxin H2, ReoT3D, Retaspimycin hydrochloride, Riferminogene pecaplasmid, Rindopepimut, Romiplostim, Ronacaleret hydrochloride, Rosuvastatin calcium, Rotigotine; Sagopilone, sALP-FcD10, SAR-245409, SCH-697243, Selumetinib, Sirolimus-eluting stent, SIR-Spheres, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tandutinib, Tasimelteon, Temsirolimus, Teriparatide
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Assessment of bitter taste of pharmaceuticals with multisensor system employing 3 way PLS regression
International Nuclear Information System (INIS)
Rudnitskaya, Alisa; Kirsanov, Dmitry; Blinova, Yulia; Legin, Evgeny; Seleznev, Boris; Clapham, David; Ives, Robert S.; Saunders, Kenneth A.; Legin, Andrey
2013-01-01
Highlights: ► Chemically diverse APIs are studied with potentiometric “electronic tongue”. ► Bitter taste of APIs can be predicted with 3wayPLS regression from ET data. ► High correlation of ET assessment with human panel and rat in vivo model. -- Abstract: The application of the potentiometric multisensor system (electronic tongue, ET) for quantification of the bitter taste of structurally diverse active pharmaceutical ingredients (API) is reported. The measurements were performed using a set of bitter substances that had been assessed by a professional human sensory panel and the in vivo rat brief access taste aversion (BATA) model to produce bitterness intensity scores for each substance at different concentrations. The set consisted of eight substances, both inorganic and organic – azelastine, caffeine, chlorhexidine, potassium nitrate, naratriptan, paracetamol, quinine, and sumatriptan. With the aim of enhancing the response of the sensors to the studied APIs, measurements were carried out at different pH levels ranging from 2 to 10, thus promoting ionization of the compounds. This experiment yielded a 3 way data array (samples × sensors × pH levels) from which 3wayPLS regression models were constructed with both human panel and rat model reference data. These models revealed that artificial assessment of bitter taste with ET in the chosen set of API's is possible with average relative errors of 16% in terms of human panel bitterness score and 25% in terms of inhibition values from in vivo rat model data. Furthermore, these 3wayPLS models were applied for prediction of the bitterness in blind test samples of a further set of API's. The results of the prediction were compared with the inhibition values obtained from the in vivo rat model
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Assessment of bitter taste of pharmaceuticals with multisensor system employing 3 way PLS regression
Energy Technology Data Exchange (ETDEWEB)
Rudnitskaya, Alisa [CESAM and Chemistry Department, University of Aveiro, Aveiro (Portugal); Kirsanov, Dmitry, E-mail: d.kirsanov@gmail.com [Chemistry Department, St. Petersburg University, St. Petersburg (Russian Federation); Blinova, Yulia [Chemistry Department, St. Petersburg University, St. Petersburg (Russian Federation); Legin, Evgeny [Sensor Systems LLC, St. Petersburg (Russian Federation); Seleznev, Boris [Chemistry Department, St. Petersburg University, St. Petersburg (Russian Federation); Clapham, David; Ives, Robert S.; Saunders, Kenneth A. [GlaxoSmithKline Pharmaceuticals, Gunnels Wood Road, Stevenage (United Kingdom); Legin, Andrey [Chemistry Department, St. Petersburg University, St. Petersburg (Russian Federation)
2013-04-03
Highlights: ► Chemically diverse APIs are studied with potentiometric “electronic tongue”. ► Bitter taste of APIs can be predicted with 3wayPLS regression from ET data. ► High correlation of ET assessment with human panel and rat in vivo model. -- Abstract: The application of the potentiometric multisensor system (electronic tongue, ET) for quantification of the bitter taste of structurally diverse active pharmaceutical ingredients (API) is reported. The measurements were performed using a set of bitter substances that had been assessed by a professional human sensory panel and the in vivo rat brief access taste aversion (BATA) model to produce bitterness intensity scores for each substance at different concentrations. The set consisted of eight substances, both inorganic and organic – azelastine, caffeine, chlorhexidine, potassium nitrate, naratriptan, paracetamol, quinine, and sumatriptan. With the aim of enhancing the response of the sensors to the studied APIs, measurements were carried out at different pH levels ranging from 2 to 10, thus promoting ionization of the compounds. This experiment yielded a 3 way data array (samples × sensors × pH levels) from which 3wayPLS regression models were constructed with both human panel and rat model reference data. These models revealed that artificial assessment of bitter taste with ET in the chosen set of API's is possible with average relative errors of 16% in terms of human panel bitterness score and 25% in terms of inhibition values from in vivo rat model data. Furthermore, these 3wayPLS models were applied for prediction of the bitterness in blind test samples of a further set of API's. The results of the prediction were compared with the inhibition values obtained from the in vivo rat model.