Evaluation of the contribution of the nasal cavity and gastrointestinal tract to drug absorption following nasal application to rats
Furubayashi, T.; Kamaguchi, A.; Kawaharada, K.; Masaoka, Y.; Kataoka, M.; Yamashita, S.; Higashi, Y.; Sakane, T.
Biological and Pharmaceutical Bulletin 30(3): 608-611
ISSN/ISBN: 0918-6158 PMID: 17329868 DOI: 10.1248/bpb.30.608
Drugs applied to the nose in in vivo physiologic condition undergo absorption from the nasal cavity and the gastrointestinal (GI) tract because drug solution in the nasal cavity, together with mucus layer, is cleared to pharynx and then to the GI tract by coordinated beat of the cilia on nasal epithelial cells. The purpose of this study was to develop evaluate the contribution of the nasal cavity and the GI tract to drug absorption following nasal application and to clarify the relation to the transepithelial permeability of the drug (the permeability to Caco-2 monolayer, PCaco-2). Male Wistar rats received intravenous, nasal, and oral drug administration and drug concentration-time profiles in plasma were determined. Fractional absorption after nasal application (F-n) and oral administration (F,,,,) were calculated from the area under the curve following intravenous injection (AUC(iv)), nasal application (AUC(n)), and oral administration (AUC(po)) as AUC(n)/AUC(iv), and AUC(po)/AUC(iv), respectively. Fractional absorption from the nasal cavity (F-NC) and the GI tract (F-GI) following nasal application was calculated as (F-n-F-po)1(1 -F-po) and F-po(1-F-NC), respectively. The shape of the curve between F-NC and PCaco-2 was similar with the one observed in the case of oral bioavailability except the curve shifted right. It is noteworthy that the relation between F-GI and Pcaco-2 showed a bell-shaped curve with peak at 10(-6) cms of PCaco-2. Highly permeable drug is primarily absorbed through the nasal mucosa before it is cleared to the GI tract. With the decrease in PCaco-2, the larger amount of the drug is cleared to the GI tract and absorption from the GI tract is increased. Poorly permeable drug, on the other hand, was absorbed neither from the nasal was nor the GI tract. These findings suggest that the primary absorption site of drug after nasal application is decided by mucociliary clearance and absorption through the nasal mucosa.