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, 5HT1B/1D agonists, as well as ergotamine, may cause vasoconstriction through stimulation of 5HT receptors on peripheral vessels. The cardiovascular effects of 20 mg oral zolmitriptan (Zomig, formerly 311C90), 2 mg oral ergotamine and the combination were assessed in a randomized double-blind, placebo-controlled crossover study in 12 healthy subjects. Pharmacodynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke volume and cardiac output using bioimpedance cardiography, high-resolution ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity. Both drugs produced small degrees of peripheral vasoconstriction, including increases in diastolic blood pressure and blood flow velocity and decreases in arterial diameter and toe-arm systolic pressure gradient. These effects were generally additive with the combination but of no clinical importance. There were 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 ergotamine. Ergotamine had no clinically important effects on zolmitriptan pharmacokinetics.
Dixon
R M
RM
Department of Clinical Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, UK.
Meire
H B
HB
Evans
D H
DH
Watt
H
H
On
N
N
Posner
J
J
Rolan
P E
PE
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004878:Ergotamine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D010080:Oxazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023303:Oxazolidinones; D011674:Pulse; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D014363:Tryptamines; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D010080:Oxazoles; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014662:Vasoconstrictor Agents; C089750:zolmitriptan; D002110:Caffeine; D004878:Ergotamine