title: Rizatriptan, a novel 5-HT1B/1D agonist for migraine: single- and multiple-dose tolerability and pharmacokinetics in healthy subjects.
abstract: Rizatriptan is a novel 5-HT1D/1B agonist for relief of migraine headache. The pharmacokinetics, metabolite profiles, and tolerability of rizatriptan were examined in a multiple-dose study in healthy subjects. Rizatriptan (N = 24) (or placebo, N = 12) was administered as a single 10 mg dose, followed 48 hours later by administration of one 10 mg dose every 2 hours for three doses on 4 consecutive days, corresponding to the maximum daily dose for a migraine attack. The AUC of rizatriptan and its active N-monodesmethyl metabolite after three 10 mg doses was approximately threefold greater than the plasma concentrations following a single 10 mg dose. Metabolite profiles were similar after single and multiple doses. Adverse events during rizatriptan were mild and transient; similar events occurred during placebo, with a somewhat reduced incidence. Diastolic blood pressure tended to increase compared with placebo (approximately 5 mmHg), particularly on the first multiple-dose day (p < .01 vs. placebo). In conclusion, rizatriptan is well tolerated by healthy subjects during multiple-dose administration, with no unexpected accumulation of drug in plasma.
authors.affiliation: Department of Clinical Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Goldberg
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.forename: K P
authors.initials: KP
authors.lastname: Vyas
authors.forename: D E
authors.initials: DE
authors.lastname: Slaughter
authors.forename: D
authors.initials: D
authors.lastname: Panebianco
authors.forename: S J
authors.initials: SJ
authors.lastname: Ermlich
authors.forename: C R
authors.initials: CR
authors.lastname: Shadle
authors.forename: M J
authors.initials: MJ
authors.lastname: Brucker
authors.forename: D A
authors.initials: DA
authors.lastname: McLoughlin
authors.forename: T V
authors.initials: TV
authors.lastname: Olah
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D014363:Tryptamines
chemical_list: D010919:Placebos; D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan