Effects of dose, pH, and osmolarity on nasal absorption of secretin in rats. II: Histological aspects of the nasal mucosa in relation to the absorption variation due to the effects of pH and osmolarity.
Nasal absorption of secretin in rats was enhanced in an acid solution, and the maximum absorption was observed at a sodium chloride solution molarity of 0.462. In order to examine reasons for the variation of absorbability caused by the change of pH and osmolarity in secretin preparations, both a pretreatment study, in which the nasal mucosa was treated with placebo prior to the administration of a secretin preparation, and a histological study were conducted in rats. The nasal absorption of secretin was determined by measuring the increased secretin of pancreatic juice. Similar profiles of nasal absorption, both after intranasal administration of secretin preparations and as a result of pretreatment effects, were obtained in studies of the effects of pH and osmolarity. However, in the pH-effect study, the absorption with the use of active preparations was observed to be significantly larger than that with the pretreatment effect below a pH of 4.79, and significantly smaller than that with the pretreatment effect at a pH of 7 to 8. The results of histological studies revealed structural changes of the epithelial cells of the nasal mucosa at pH 2.94, and shrinkage of epithelial cells was observed at a sodium chloride solution molarity of 0.462.
Ohwaki
T
T
Research Laboratories of Pharmaceutical Development, Eisai Co., Ltd., Gifu, Japan.
Ando
H
H
Kakimoto
F
F
Uesugi
K
K
Watanabe
S
S
Miyake
Y
Y
Kayano
M
M
D000042:Absorption; D000818:Animals; D006863:Hydrogen-Ion Concentration; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000493:pharmacokinetics*
D012633:Secretin