PERIPHERAL VASCULAR EFFECTS AND PHARMACOKINETICS OF THE ANTIMIGRAINE COMPOUND, ZOLMITRIPTAN, IN COMBINATION WITH ORAL ERGOTAMINE IN HEALTHY-VOLUNTEERS

Members of the new class of antimigraine compounds, 5HT(1B/1D) agonist s, as well as ergotamine, may cause vasoconstriction through stimulati on of 5HT receptors on peripheral vessels. The cardiovascular effects of 20 mg oral zolmitriptan (Zomig(TM), formerly 311C90), 2 mg oral erg otamine and the combination were assessed in a randomized double-blind , placebo-controlled crossover study in 12 healthy subjects. Pharmacod ynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke vol ume and cardiac output using bioimpedance cardiography, high-resolutio n ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity. Both drugs produced small degr ees of peripheral vasoconstriction, including increases in diastolic b lood pressure and blood flow velocity and decreases in arterial diamet er and toe-arm systolic pressure gradient. These effects were generall y additive with the combination but of no clinical importance. There w ere no significant changes in cardiac output, stroke volume heart rate or ECG. Zolmitriptan, at eight times the Likely therapeutic dose, was generally well tolerated both alone and in combination with ergotamin e. Ergotamine had no clinically important effects on zolmitriptan phar macokinetics.