title: Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine.
abstract: Rizatriptan is a potent, oral 5-HT(1B/1D) agonist with a rapid onset of action being investigated for the acute treatment of migraine. This study examined the clinical and pharmacolinetic interaction between rizatriptan and the selective serotonin reuptake inhibitor, paroxetine. In this two-period crossover study, 12 healthy young subjects (6 males and 6 females) received 1 mg rizatriptan following 14 days of treatment with placebo or paroxetine (20 mg once daily). Plasma was sampled for rizatriptan and N-monodesmethyl rizatriptan, a minor but active metabolite of rizatriptan. Safety evaluations included monitoring for adverse events, vital signs, and visual analog scale assessment of mood. Plasma levels of rizatriptan and N-monodesmethyl rizatriptan were not altered when rizatriptan was administered with paroxetine compared to the placebo. Clinically, coadministration of rizatriptan with paroxetine was well tolerated. Blood pressure, heart rate, and temperature changes during the observation period did not differ to a clinically significant degree when rizatriptan was administered with paroxetine compared to the placebo. No effects on mood occurred following treatment with the combination compared to rizatriptan alone. Adverse events following rizatriptan administration with paroxetine were similar to those reported when rizatriptan was given with the placebo.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Goldberg
authors.forename: R C
authors.initials: RC
authors.lastname: Lowry
authors.forename: D G
authors.initials: DG
authors.lastname: Musson
authors.forename: K L
authors.initials: KL
authors.lastname: Birk
authors.forename: A
authors.initials: A
authors.lastname: Fisher
authors.forename: M E
authors.initials: ME
authors.lastname: De Puy
authors.forename: C R
authors.initials: CR
authors.lastname: Shadle
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014363:Tryptamines
chemical_list: D017374:Paroxetine; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan