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 variable absorption and limited bioavailability. Together with its abundant vascularization, relative mucosal thickness stability, and low clearance rates, the upper nasal space harnesses the benefits of nasal delivery to potentially maximize
drug efficacy.