Pharmacokinetic analysis of drug absorption following nasal application to rats
7 , 2017-04 , 岡山実験動物研究会
Since a drug applied to the nose in an in vivo physiologic condition is translocated to the gastrointestinal (GI) tract by mucociliary clearance (MC), the drug undergoes absorption both from the nasal cavity and from the GI tract. The detailed MC of the rat was examined, using inulin as a marker of the applied solution. Inulin disappeared monoexponentially from the nasal cavity, indicating that the MC can be assumed to follow first-order kinetics. In the proposed kinetic model, the fractional absorption of the drug following nasal application is predicted as the sum of fractional absorption from the nasal cavity and fractional absorption from the GI tract, both of which are estimated indirectly from the permeability to the Caco-2 monolayer. This kinetic model is the first estimation system for nasal drug absorption based on drug disposition after nasal application and is useful for the development of nasal dosage forms.