Rizatriptan, a novel 5-HT1B/1D agonist for migraine: single- and multiple-dose tolerability and pharmacokinetics in healthy subjects

• Published in: Journal of clinical pharmacology Vol. 40; no. 1; p. 74
• Main Authors: Goldberg, M R, Lee, Y, Vyas, K P, Slaughter, D E, Panebianco, D, Ermlich, S J, Shadle, C R, Brucker, M J, McLoughlin, D A, Olah, T V
• Format: Journal Article
• Language: English
• Published: England 01.01.2000
• Subjects: Adult; Blood Pressure - drug effects; Double-Blind Method; Female; Humans; Male; Middle Aged; Placebos; Serotonin Receptor Agonists - administration & dosage; Serotonin Receptor Agonists - adverse effects; Serotonin Receptor Agonists - pharmacokinetics; Time Factors; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - pharmacokinetics; Tryptamines
• ISSN: 0091-2700
• DOI: 10.1177/009127000004000110

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.