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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Clinical pharmacokinetics of frovatriptan.

OBJECTIVE: To review available data on the clinical pharmacokinetics of frovatriptan. BACKGROUND: Preclinical data suggest that the pharmacokinetic profile of frovatriptan may differ from that of the currently available triptans. METHODS: Studies of healthy volunteers, subjects with renal or hepatic impairment, elderly subjects, and patients with migraine during and between attacks were reviewed. RESULTS: Oral bioavailability of frovatriptan is 22% to 30%, and although the time to maximum concentration is typically 2 to 3 hours, approximately 60% to 70% of plasma maximum concentration is achieved within 1 hour of dosing. Frovatriptan distributes into erythrocytes, with binding reversible and time dependent. The relatively long terminal elimination half-life (about 26 hours) confers good systemic exposure and may produce a long duration of therapeutic action, thus reducing migraine recurrence and the need for redosing. Systemic exposure to frovatriptan generally correlates with dose between 1 and 100 mg. Blood and plasma frovatriptan concentrations are consistently higher in females, but there is no need to adjust dose according to gender. Pharmacokinetics are essentially unaffected by food and were predictable after repeat dosing; steady state is approached in about 4 to 5 days. Pharmacokinetics were changed only slightly in subjects with renal impairment or mild-to-moderate hepatic impairment, elderly individuals, and during migraine attacks. Frovatriptan is principally metabolized by the CYP1A2 isoenzyme of cytochrome P-450 and is cleared by the kidney and liver, each having sufficient capacity to compensate for impairment of the other. CONCLUSIONS: Frovatriptan can be taken without regard for food intake, and because of the large therapeutic margin and shallow dose-response curve, there is no need for dosage adjustment in the elderly, in women taking a combined oral contraceptive, in patients with mild-to-severe renal impairment, mild-to-moderate hepatic impairment, or according to gender. The long duration of exposure may reduce the likelihood of early migraine recurrence.[1]


  1. Clinical pharmacokinetics of frovatriptan. Buchan, P., Keywood, C., Wade, A., Ward, C. Headache. (2002) [Pubmed]
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