胰岛素口腔喷雾制剂在大鼠及家兔体内的药效学和药动学研究

Pharmacodynamic and pharmacokinetic studies of an insulin buccal spray formulation in rats and rabbits

目的 探索胰岛素经口腔给药的可能性。方法 以大鼠和家兔为动物模型 ,进行胰岛素口腔喷雾制剂的体内降糖实验 ,同时测定了口腔给药后的胰岛素水平变化。以皮下注射胰岛素溶液为对照 ,计算口腔给药的药理相对生物利用度 ,以及相对生物利用度。用 3P87程序拟合了大鼠和家兔口腔给药及皮下注射给药的药动学参数。结果 以皮下注射胰岛素溶液为对照 ,胰岛素口腔给药后 ,大鼠及家兔口腔给药的药理相对生物利用度分别为 30 .8%和 40 .3 %。相对生物利用度分别为2 2 .50 %及 2 3 .89%。胰岛素口腔喷雾剂经家兔给药的血药峰浓度及相对生物利用度均比大鼠高。大鼠口腔给药及皮下注射给药、家兔口腔给药及皮下注射给药的药 时曲线均符合权重为 1 /C/C的一室模型。大鼠与家兔皮下和口腔给药的吸收速率常数Ka有显著性差别 ,胰岛素喷雾剂经大鼠或者家兔口腔给药时的吸收较皮下注射给药时的吸收快。结论 胰岛素口腔喷雾剂经口腔喷雾后 ,起效快 ,生物利用度较高 ,这证明了胰岛素制剂在口腔部位吸收的可能性 。

OBJECTIVE: To investigate feasibility of the insulin absorption via the buccal mucous of an buccal spray formulation. METHODS: The hypoglycemic effect and the changes of insulin concentration in vivo of an insulin buccal spray formulation in rats and rabbits were investigated. Compared with subcutaneous administration of insulin solution, the relative pharmacological bioavailability and the relative bioavailability of insulin buccal spray were determined and the pharmacokinetic parameters were calculated by means of 3P87. RESULTS: The relative pharmacological bioavailabilities of insulin spray in rats and rabbits were 30.8% and 40. 3%, respectively. According to the data of insulin concentration, the relative bioavailabilities of insulin spray in rats and rabbits were 22.5% and 23.9%, respectively. The concentration-time data of buccal and sc adminstration of insulin in rats and rabbits were all fitted to one compartment-model with a weight of 1/C/C. The absorption of buccal insulin spray was found more rapid than that of subcutaneous administration. The absorption and elimination of buccal insulin spray in rabbits were rapid than those in rats. CONCLUSION: It showed that the insulin buccal spray formulation played a role in reducing the blood glucose level and increasing the plasma insulin concentration. This proved the possibility of insulin delivery via the buccal route.