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Nasal administration technique Using PT-141 nasal spray: Blow nose gently (clear passages) Prime pump (1-2 test sprays into air) Tilt head slightly forward (not back) Insert nozzle into nostril (don't deep) Spray while breathing in gently 2-3 sprays per nostril typically Alternate nostrils Avoid sniffing hard (keeps in nasal tissue) Wait 2-3 minutes between sprays Absorption through nasal mucosa: PT-141 absorbed across nasal lining Enters bloodstream directly Bypasses stomach/liver (like injection) But: Lower bioavailability (~30%) Hence need 2-3x higher dose Nasal spray pros/cons: When to choose nasal: Needle phobic Value convenience highly Don't mind using 2-3x more peptide Want slightly faster onset Traveling (easier to transport) When to choose injection: Want cost efficiency Comfortable with injections Prefer guaranteed absorption Limited PT-141 supply Already using other injectable peptides Managing PT-141 side effects Minimizing nausea and other reactions

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20 GojkovicS.KrezicI.VranesH.ZizekH.DrmicD.Horvat PavlovK.et al (2021a)

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