Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

Vincent Martin, John Hoekman, Sheena K. Aurora and Stephen B. Shrewsbury

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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 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.

To cite: Martin, V.; Hoekman, J.; Aurora, S.K.; Shrewsbury, S.B. Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space. J. Clin. Med. 2021, 10, 2468.