The relevance of nasal physiology to the design of drug absorption studies

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