鲑鱼降钙素大鼠肺部给药系统的研究

Study on pulmonary delivery system of salmon calcitonin in rats

目的 :研究多肽类药物鲑鱼降钙素 (sCT)肺部给药后体内的血药浓度改变及不同渗透促进剂的促渗作用。方法 :采用放射免疫分析法测定sCT溶液经大鼠肺部给药后的体内血清降钙素浓度 ,同时比较不同给药方式、不同渗透促进剂及不同 pH值下的血药浓度 ,并与肌内注射对照 ,计算不同条件下sCT的相对生物利用度 (Fr)。 结果 :与肌内注射相比 ,2 μg·kg-1的sCT溶液经肺部给药的Fr值为 12 1.0 % ,渗透促进剂苄泽 78、牛磺胆酸钠、卵磷脂、壳聚糖、辛酸钠及酸性环境 (pH3.0 )均可显著增加sCT的肺部吸收。结论

Objective: To study the serum calcitonin(CT) levels in vivo after pulmonary delivery to rats and the effects of absorption enhancers. Methods: Salmon calcitonin (sCT) solution was delivered by intramuscular injection or intratracheal administration to rats. The absorption of sCT was determined by radioimmunoassay method. Changes in serum drug levels after the pulmonary administration of sCT with various absorption enhancers or in different pH conditions were investigated. Results: Compared with intramuscular administration, the relative bioavailability of sCT solution (2 μg·kg -1 ) given by intratracheal route was 121.0%. Transpulmonary absorption of sCT solution, with some absorption enhancers (Brij78, sodium cholate, lecithin, chitosan and sodium caprylate) or under acidic conditions (pH3.0), was significantly greater than the values obtained in controls. Conclusion:sCT solution showed higher bioavailab