311C90 (ZOLMITRIPTAN-ASTERISK), A NOVEL CENTRALLY AND PERIPHERAL ACTING ORAL 5-HYDROXYTRYPTAMINE-1D AGONIST - A COMPARISON OF ITS ABSORPTION DURING A MIGRAINE ATTACK AND IN A MIGRAINE-FREE PERIOD

The oral absorption of a 10-mg oral dose of the novel 5-hydroxytrptami ne (5HT(1D)) agonist, 311C90, was compared during a moderate or severe migraine headache and in a migraine-free period in an open, two-perio d study. The safety and efficacy of 311C90 in acute migraine were also assessed. Twenty patients attended the clinics during a moderate or s evere migraine attack and 18 patients returned for a second dose in a migraine-free period. 311C90 was less rapidly absorbed during a migrai ne attack compared to the migraine-free period, consistent with gastri c stasis during a migraine attack. The median area under the curve (AU C) was 15/7 ng/mlh lower during a migraine (median AUG: 18.4 ng/ml.h, range: 0-60.8 ng/ml.h) compared to the migraine-free period (median AU C:33.4 ng/ml.h, range 9.4-79.5 ng/ml.h) (95% confidence interval: 6.9, 25.3) and the time to reach maximum plasma concentration was delayed ( n=18). Eleven out of 20 patients experienced a significant improvement in migraine headache intensity at 2h post-dose. Plasma 311C90 concent rations were generally higher in those patients who responded to treat ment with 311C90 in the plasma, but there was one patient with no quan tifiable 311C90 in the plasma whose headache improved. Minor adverse e xperiences were reported in 11 out of 20 patients during a migraine at tack and in 11 out of 18 patients outside an attack. They occurred sho rtly following drug administration and were of short duration, but the ir occurrence did not appear to be related to plasma 311C90 concentrat ion. There were no clinically significant changes in blood pressure or 12-lead ECG during the assessment period.