Journal of Clinical Medicine Review Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space Vincent Martin 1, John Hoekman 2, Sheena K. Aurora 3 and Stephen B. Shrewsbury 4,* 1 University of Cincinnati Headache and Facial Pain Center, Cincinnati, OH 45219, USA;
[email protected] 2 Research & Development, Impel NeuroPharma, Seattle, WA 98119, USA;
[email protected] 3 Medical Affairs, Impel NeuroPharma, Seattle, WA 98119, USA;
[email protected] 4 Clinical Development, Impel NeuroPharma, Seattle, WA 98119, USA * Correspondence:
[email protected] Abstract: The acute treatment of migraine requires effective drugs that are well tolerated and provide rapid and consistent pain relief. Oral tablets are the most commonly used acute treatment for migraine; however, their effectiveness is limited by the rate of gastrointestinal (GI) tract absorption and first-pass hepatic metabolism, and they may not be ideal for patients experiencing GI motility issues. Nasal delivery is an attractive alternative route as it may circumvent GI tract absorption, avoid first-pass metabolism in the liver, and potentially reduce the frequency of GI adverse events. The large surface area and high vascularity within the nose may permit rapid absorption of therapeutics into the systemic circulation, allowing for rapid onset of action. However, the site of drug deposition (upper versus lower nasal cavity) may influence drug pharmacokinetics. Most approved nasal migraine therapies target the lower nasal space where the epithelium is less permeable, and they may be quickly cleared away due to increased ciliary function or dripping from the nose or swallowing, resulting in Citation: Martin, V.; Hoekman, J.; variable absorption and limited bioavailability.