Abstract
Enhancing effect of the pretreatment with 1-dodecylazacycloheptan-2-one (Azone) on the absorption of salicylic acid from keratinized oral mucosa was investigated in vivo using a hamster cheek pouch. The absorption was significantly increased after the 4 h pretreatment with Azone-emulsion when the pretreatment medium contained Azone above 0.2%. The enhancement was observed at all pH conditions examined irrespective of the degree of dissociation of the drug. The apparent disappearance rate constant of salicylic acid, calculated from the time course of the sum of remaining amounts of the drug in both the luminal fluid and the tissue, in Azone-pretreated cheek pouch was approximately 2.7 times larger than in the non-treated one. The pharmacokinetic analysis of the plasma concentration of salicylic acid after the intra-cheek-pouch administration revealed that Azone pretreatment enhanced the absorption i.e., increased the absorption rate constant and shortened the mean absorption time by one-fifth, and brought the peak plasma concentration approximately twice higher. The enhanced absorption after 1 h pretreatment with 5% Azone-emulsion diminished with the lapse of time and the barrier function of the cheek pouch was completely recovered within 6 h after the removal of the Azone-emulsion.
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