DRUG EFFECTS ON IN-VIVO NASAL CLEARANCE IN RATS

被引:21
作者
DONOVAN, MD
ZHOU, MP
机构
[1] The University of Iowa, College of Pharmacy, Iowa City
关键词
MUCOCILIARY CLEARANCE; NASAL DRUG DELIVERY; TRIPELENNAMINE; LIDOCAINE; BACITRACIN; NEOMYCIN; PILOCARPINE; MORPHOLOGY;
D O I
10.1016/0378-5173(94)00274-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A simple in vivo method to study drug induced changes in nasal mucociliary clearance patterns has been developed using FluoSpheres (R), fluorescent latex particles, as clearance markers in rats. The marker cleared from the nasal cavity can be collected from the nasopharyngeal area of the oral cavity and easily measured using a fluorescence spectrophotometer. Several compounds whose effects on ciliary motility have been previously studied in vitro, i.e., tripelennamine HCl, lidocaine HCl, bacitracin, neomycin sulfate, and pilocarpine nitrate, were investigated in order to validate the new in vivo technique. Clearance in rats exposed to normal saline was shown to follow a pseudo-first order pattern. Similar first order clearance patterns were observed 24 h after exposure to drug solutions which have been shown to cause reductions in ciliary beat frequency (CBF) or mucociliary clearance (tripelennamine HCl, lidocaine HCl, bacitracin) in vitro, yet the clearance rates in vivo were usually reduced. The clearance rates returned to normal within 48 h except in the case of lidocaine HCl. For compounds in which increases in CBF were observed in vitro (pilocarpine nitrate), a statistically significant increase in nasal clearance was observed 24 h after drug exposure. The ability of the in vitro method to predict the reversibility of drug induced effects was not well correlated with the results observed in vivo. It appears that homeostatic control mechanisms present in the whole animal temper some drug effects on ciliary motility, especially when morphologic changes in the cilia appear to be responsible for the reduction in CBF. This new in vivo model enables both long term changes and the time course of recovery in nasal clearance to be monitored in a single animal, thus enabling better predictions regarding drug effects on nasal clearance to be made.
引用
收藏
页码:77 / 86
页数:10
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