Biol. Pharm. Bull. 30(3) 608—611 (2007)

researchers within the last few decades because of its great potential utility for rapid drug delivery. It offers an attractive alternative for drugs that have limited oral bioavailability, are destroyed by gastrointestinal (GI) fluid, or are highly susceptible to hepatic first pass or gut-wall metabolism. Nasal drug delivery also offers the convenience and safety of noninvasiveness. In addition, nasal drug administration results in quick onset of action as compared with oral and transdermal administrations. The respiratory epithelium is covered with a mucous layer. Some respiratory epithelial cells possess cilia on their surface. These cilia beat in coordinated fashion to transport the mucous layer to the nasopharynx, where it is swallowed. The combined action of mucus layer and cilia is called mucociliary clearance (MC). It is an important nonspecific defense mechanism of the respiratory tract to protect the body against noxious inhaled materials. Due to MC, drugs applied to the nasal cavity are cleared to the nasopharynx and, thereafter, to the GI tract, together with the mucus layer. Some fraction of nasally administered drug undergoes absorption from the GI tract. Although the contribution of the nose and GI tract to drug absorption after nasal application has been reported, no information on its relation to membrane permeability of the drug is available at present. Hirai et al. reported a series of studies on nasal drug absorption. In their reports, rats were investigated in the supine position under anesthesia with the esophagus ligated to avoid clearance of drug from the nasal cavity. Since their reports, much research has been done utilizing the same surgical procedure. This procedure is reasonable in studies aimed at clarifying the barrier characteristics of the nasal mucosa. However, this experimental situation is quite different from the physiologic condition. It is not feasible to investigate MC in rats in which the esophagus is ligated. Additionally, the position of the animal during the absorption study is likely important. Movement of the drug by mucociliary clearance may differ in the supine position as compared with that in the normal prone position. The aim of this research was to evaluate nasal and intestinal absorption following nasal drug administration. For this purpose, drug absorption following nasal application was investigated in the normal physiologic condition. The relation of the fractional absorption of the drug from the nasal cavity and from the GI tract to Caco-2 permeability (PCaco-2) was clarified and discussed here in.