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      Efficacy and pharmacokinetic activity of frovatriptan compared to rizatriptan in patients with moderate-to-severe migraine

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          Abstract

          Background

          Migraine is a painful neurological disorder that affects over 10% of the general population. Frovatriptan and rizatriptan are antimigraine agents belonging to the triptan class. Although previous studies have independently compared the efficacy of these agents, contemporaneous data examining both pharmacokinetic (PK) properties and efficacy in parallel have not previously been available.

          Materials and methods

          In this single-center double-blind study, 18 subjects (ten female) were treated for a single migraine attack with frovatriptan 2.5 mg or rizatriptan 10 mg. Plasma concentrations were measured predose and at 2, 4, 6, 12, 24, 48, and 72 hours after drug administration. The primary end point of this study was to evaluate the association between PK parameters and efficacy measures and recurrence rate. Secondary end points were pain-free and pain-relief episodes at 2 and 4 hours, recurrent episodes within 48 hours, and cumulative hazard of recurrence within 72 hours.

          Results

          At baseline, approximately 17% of patients had mild migraine, while 83% had moderate–severe migraine. Although the time to maximum concentration was similar for both drugs (2.7 versus 2.3 hours), the terminal half-life for frovatriptan was longer than rizatriptan (29.3 versus 3.2 hours, P<0.0001). The proportion of patients who were pain-free at 4 hours without rescue medication was higher in the frovatriptan-treated group, (38.9 versus 5.6%, P=0.045). The cumulative hazard of recurrence over 72 h was reduced by frovatriptan compared to rizatriptan-treated patients (log-rank test, P=0.04). Pain-free and pain-relief episodes for the study period were positively correlated with the concentration:maximum concentration (C max) ratio for frovatriptan ( r=0.52, P=0.028), but not rizatriptan. Recurrence rate was negatively correlated with the concentration:C max ratio for both frovatriptan ( r=−0.96, P=0.0024) and rizatriptan ( r=−0.98, P=0.0004). Fewer adverse events were observed for frovatriptan compared to rizatriptan (one versus eight, P=0.021).

          Conclusion

          This pilot study indicates that a similar extent of initial pain relief is afforded by both triptans in migraine treatment. The longer duration of action of frovatriptan parallels and correlates with its PK profile.

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          Most cited references 26

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          The International Classification of Headache Disorders: 2nd edition.

            (2003)
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            Headache and comorbidity in children and adolescents

            Headache is one of the most common neurological symptom reported in childhood and adolescence, leading to high levels of school absences and being associated with several comorbid conditions, particularly in neurological, psychiatric and cardiovascular systems. Neurological and psychiatric disorders, that are associated with migraine, are mainly depression, anxiety disorders, epilepsy and sleep disorders, ADHD and Tourette syndrome. It also has been shown an association with atopic disease and cardiovascular disease, especially ischemic stroke and patent foramen ovale (PFO).
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              Triptan therapy in migraine.

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2014
                21 July 2014
                : 8
                : 983-992
                Affiliations
                [1 ]Department of Neuroscience, University of Turin, Turin, Italy
                [2 ]Primula Multimedia SRL, Pisa, Italy
                Author notes
                Correspondence: Colin Gerard Egan, Primula Multimedia SRL, 22/B Via Giuseppe Ravizza, Ospedaletto, Pisa 56121, Italy, Tel +39 050 965 6242, Fax +39 050 316 3810, Email cegan@ 123456primulaedizioni.it
                Article
                dddt-8-983
                10.2147/DDDT.S61295
                4112748
                © 2014 Savi et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

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