Effect of dose, pH, and osmolarity on nasal absorption of secretin in rats. III. In vitro membrane permeation test and determination of apparent partition coefficient of secretion.
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 predict how changes in the secretin molecule would affect its absorption through the nasal mucosa independently of structural changes in the epithelial membrane, an artificial membrane permeation test was conducted, and the apparent partition coefficient between octanol and a test solution was determined. The concentration of secretin was measured using high performance liquid chromatography. The amount of secretin that permeated through an artificial membrane was hardly affected by changes in pH, which suggest that the size of the secretin molecule was not changed. The apparent partition coefficient, however, increased as the pH of the test solution rose from 3.81 to 7.0, which suggested that the hydrophobicity of secretin was enhanced. In relation to the osmolarity of the test solution, the amount of permeation was hardly affected by the concentration of sodium chloride, but the partition coefficient increased with the concentration of the sodium chloride solution. It was supposed that the size of the secretin molecule was not changed in spite of the increasing hydrophobicity, and the nasal absorption of secretin at a sodium chloride molarity of 0.462 was dependent on a change in the epithelial cells. When sorbitol was used as an osmoregulatory agent, the apparent partition coefficient hardly varied as the osmolarity of the solution was increased, whereas the amount of permeation decreased, and these findings reflected the nasal absorption in rats.
Ohwaki
T
T
Ishii
M
M
Aoki
S
S
Tatsuishi
K
K
Kayano
M
M
D000042:Absorption; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D009297:Nasal Mucosa / Q000378:metabolism*; D009994:Osmolar Concentration; D010539:Permeability; D051381:Rats; D012633:Secretin / Q000493:pharmacokinetics*; D012995:Solubility
D008567:Membranes, Artificial; D012633:Secretin