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• W2076085459 startingPage "1007" @default.
• W2076085459 abstract "The purpose of this study is to propose a kinetic model to predict the absorption of nasally applied drugs from their permeability to the Caco-2 monolayer (PCaco-2). Since a drug applied to the nose in an in vivo physiologic condition is translocated to the gastrointestinal (GI) tract by coordinated beats of cilia (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. From the disappearance of inulin, the first order rate constant for MC (kMC) was calculated as 0.0145 min−1. In the proposed kinetic model, the fractional absorption of the drug following nasal application is predicted as the sum of FNC (fractional absorption from the nasal cavity) and FGI (fractional absorption from the GI tract), both of which are estimated indirectly from PCaco-2. FNC is calculated according to the equation, ka/(ka+kMC), where ka is the absorption rate constant. Nasal drug absorption is assumed to follow first order kinetics. The ka of four drugs was initially calculated from kMC and their FNC; thereafter, the linear relationship between ka and PCaco-2, from which ka is predicted, was determined. FGI is calculated as Fp.o.(1−FNC), where Fp.o. is fractional absorption after oral administration. Fp.o. was predicted from the previously determined sigmoid curve between Fp.o. and PCaco-2. The proposed 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." @default.
• W2076085459 created "2016-06-24" @default.
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• W2076085459 date "2007-01-01" @default.
• W2076085459 modified "2023-10-11" @default.
• W2076085459 title "Kinetic Model to Predict the Absorption of Nasally Applied Drugs from in Vitro Transcellular Permeability of Drugs" @default.
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• W2076085459 doi "https://doi.org/10.1248/bpb.30.1007" @default.
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