鼻粘膜纤毛清除系统对鼻内给药途径的影响

Influence of nasal mucociliary system on intranasal administration

本文使用硫酸庆大霉素研究鼻兔粘膜纤毛清除系统对鼻粘膜吸收药物的影响。对兔动物模型封闭鼻咽腔（无纤毛清除系统的作用）和不封闭鼻咽腔（有纤毛清除系统的作用），然后使用庆大霉素鼻内给药，测定０－１８０分钟的血清药物浓度，结果发现鼻粘膜纤毛清除系统可减少鼻粘膜对药物的吸收，使吸收率和曲线下的吸收面积（ＡＵＣ）分别降低２５．１％和１８．２％。为减少纤毛清除系统的影响，作者设计将乙酰半胱氨酸加入滴鼻剂中以拮抗纤毛系统的活动，用鼻腔喷雾药液来代替滴鼻以增加鼻粘膜非纤毛区药物的附集。结果发现两者有明显促进鼻粘膜吸收药物的功能，前者使最大吸收和ＡＵＣ分别提高１８％和１０．７％，后者使吸收增加１．５一１．６倍。

Abstract The nfluence of nasal mucociliary system on intranasal uptak. of gentamycin sulfate was studied.The nasopharynxes of rabbits were closed to stop the fuction of mucociliary system. On the other group rabbits remained the mucociliary fuction. The rabbits were given nasal drip of gentamycin and the serum levels of gentamycin from O to 180 minuts after applying the drug were determined.It was found that nasal mucociliary fuction reduced the intranasal absorption of the drug and let the highest absorbing rate and area under the curve(AUC)decrease 25.1%and 18.2% respectively. To reduce the undesirable effect of nasal mucociliary system acetylcys- teine was mixed into the gentamycin drip,and nasal drip of the drug was replaced by nasal spray to increase the absorption of the drug in non-ciliary area of nasal cav- ity. It was shown that both of the two could promote the nasal mucosa to absorb the drug. The former make the highest intranasal absorption and AUC increased 18.0% and 10.7%respectively and the later increased 1.5-1.6 times.