New drug delivery options for migraine.

Migraine is characterized by attacks of moderate to severe intensity headache, associated with some combination of severe disability, autonomic dysfunction such as gastric stasis, poor absorption from the small bowel, and associated symptoms such as nausea, vomiting, phonophobia, photophobia and worsening with exertion [1,2]. Oral medications may not be ideally suited for those migraineurs with nausea, vomiting and poor gastrointestinal absorption and an non-oral route of delivery may be optimal in such patients. Injection and nasal delivery systems for migraineurs do exist and they bypass gastrointestinal absorption; however, these approaches may be associated with limiting adverse events and/or lack of efficacy for some patients [3,4]. The recent developments in drug delivery systems presented here are either entering, in the middle of, or have completed Phase III development. Each may offer clinical benefits including a convenient, non invasive delivery of medication that bypasses the GI tract and hepatic first-pass metabolism, allowing for a rapid and consistent response to treatment with fewer adverse events. These delivery devices may prove to be the route of choice for patients experiencing symptoms consistent with gastrointestinal dysfunction (nausea, vomiting and gastric stasis) associated with migraine. Intranasal delivery (OptiNoseTM) The use of a novel, breath-actuated device for intranasal delivery of a powder formulation of sumatriptan in acute migraine treatment was evaluated in one Phase I and one Phase II trial [5,6]. The use of this bidirectional delivery system named OptiNoseTM (Optinose US Inc., PA, USA) has shown improved deposition to the olfactory mucosa, which is essential for rapid systemic absorption [7]. Traditional nasal delivery methods deliver a significant part of the dose anterior to the nasal valve and the fraction that does bypass the nasal valve is largely swallowed. By contrast, the OptiNose device consists of a mouthpiece and a sealing nozzle that fits into one nostril; blowing into the device causes the soft palate to close, isolating the nasal cavity. As the patient continues to blow out, the device is triggered, releasing the drug into the air flow and carrying it deep into the nasal cavity. The air flow carries the drug through a communication between the two nasal passages and forwards in the other nostril towards the entrance. A Phase I study showed a faster and more extensive systemic absorption, probably due to better absorption across the nasal mucosa, than the existing sumatriptan nasal spray device [5]. The Phase II study was designed to evaluate the efficacy and Michail Vikelis