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

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 (Cmax) ratio for frovatriptan (r=0.52, P=0.028), but not rizatriptan. Recurrence rate was negatively correlated with the concentration:Cmax 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.