The parenteral administration of drugs is often associated with compli
cations. For example, low patient acceptance of these routes leading t
o non-compliance can be a particular risk when self-administration is
needed for chronic therapy. Consequently, alternatives such as the nas
al, buccal, ocular and vaginal routes have been considered, e.g. for s
ystemic peptide and protein drug delivery. This review focusses on the
relevance of the intranasal administration of drugs, peptides and vac
cines, and looks at some physiological factors that present a barrier
to the use of this route. A brief overview is given of the pharmacokin
etics of drugs administered to the nasal cavity, including some of the
physiological factors that may influence the kinetics, and on the maj
or intranasal drug absorption models used today. Physiological factors
highlighted are (1) mucus and mucociliary clearance; (2) enzymatic de
gradation; (3) immunological factors; (4) blood flow and (5) depositio
n of drugs in the nasal cavity.