Rapid oral transmucosal absorption of sumatriptan, and pharmacodynamics in acute migraine

(1) To determine whether sumatriptan can be absorbed across the oral mucosa, and, if so; then (2) to describe its pharmacokinetics; and (3) to investigate whether there are pharmacodynamic correlates of such pharmacokinetics in patients experiencing migraine attacks.

Two clinical trials. The first, in normal volunteers, compared the pharmacokinetic performance of a lingual spray (LS) formulation of sumatriptan (2 dose sizes, one of which in both the fed and fasted state) with an orthodox 50-mg sumatriptan tablet. The second clinical trial, in a patient population enriched by documenting suboptimal response to an initial 50-mg sumatriptan tablet, was a multiple-attack, crossover, fixed dose-order, open-label comparison of sumatriptan administered by LS (up to 3 different dose sizes) and a 100-mg sumatriptan tablet.

The LS formulations resulted in double-peaked time-plasma concentration curves that are consistent with absorption of sumatriptan across the oral mucosa. The first T(max) was usually about 10-15 minutes. In the enriched patient population, this corresponded with evidence of earlier efficacy for the LS in comparison with a 50-mg tablet; the lower dose size for the former was consistent with oral mucosal drug absorption, and evasion of first-pass metabolism.

The initial pharmacokinetics of LS approximate to those of a subcutaneous injection, albeit some fraction of these doses is also swallowed. These pharmacokinetics correspond with earlier effectiveness of LS in comparison with a 50-mg sumatriptan tablet, and at lower dose, in an enriched, relevant patient population. These initial studies support further development of this innovative formulation of sumatriptan and this new route of administration.