Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine

Rizatriptan is a potent, oral 5-HT1B/1D agonist with a rapid onset of actio n being investigated for the acute treatment of migraine. This study examin ed the clinical and pharmacokinetic interaction between rizatriptan and the selective serotonin reuptake inhibitor, paroxetine. In this two-period cro ssover study, 12 healthy young subjects (6 males and 6 females) received 10 mg rizatriptan following 14 days of treatment with placebo or paroxetine ( 20 mg once daily). Plasma was sampled for rizatriptan and N-monodesmethyl r izatriptan, ct minor but och;ire metabolite of rizatriptan. Safety evaluati ons 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 paroxet ine compared to the placebo. Clinically, coadministration of rizatriptan wi th paroxetine was well tolerated Blood pressure, heart rate, and temperatur e changes during the observation period did not differ to a clinically sign ificant degree when rizatriptan was administered with paroxetine compared t o the placebo. No effects on mood occurred following treatment with the com bination compared to rizatriptan alone. Adverse events following rizatripta n administration with paroxetine were similar to those reported when rizatr iptan was given with the placebo. (C) 1999 the American College of Clinical Pharmacology.