胰岛素口腔黏膜喷雾剂在四氧嘧啶致糖尿病兔体内的药动学研究

Pharmacokinetics of Oral Mucosa Spraying Agent of Insulin in Patients with Alloxan Diabetes

目的:考察胰岛素口腔黏膜喷雾剂在糖尿病模型兔体内的药动学。方法:将36只家兔以四氧嘧啶造模成功后分为生理盐水组、胰岛素舌下喷雾给药组(低、中、高剂量)、中性胰岛素组和胰岛素皮下给药组,单剂量给药后,放免法测定胰岛素血清浓度,并计算药动学参数。结果:与生理盐水组比较,低、中、高剂量胰岛素舌下喷雾给药组的tmax和Cmax值均明显升高(P<0·01),AUC值明显增加(P<0·05或P<0·01),平均生物利用度为6·6%。胰岛素给药剂量与血中胰岛素AUC值间均呈显著线性相关(P<0·01)。结论:口腔黏膜喷雾剂可作为胰岛素皮下给药的有效替代给药途径。

OBJECTIVE： To investigate the pharmacokinetics of oral mucosa consperge agent of insulin in rabbits with alloxan diabetes. METHODS： A total of 36 rabbits were administered with alloxan for modeling. The rabbits were then assigned to normal sodium （NS） group, oral mucosa spraying agent groups （low, middle, and high dosages）, neutral insulin group, and subcutaneous insulin group. After single dose administration of corresponding drugs, serum concentrations of insulin were monitored by radioimmunity. RESULTS： As compared with NS group, in oral mucosa spraying agent groups （low, middle, and high dosages）, t and C elevated significantly （ P 〈 0.01）, and AUC increased significantly （ P 〈 0.05, or P 〈 0.01） with an average bioavailability of 6.6%. There was a significant linear correlation between the administration dosage of insulin and serum insulin AUC level（P〈0.01） . CONCLUSION： The oral mucosa spraying method serves as an effective substitutive route for the subcutaneous administration of insulin.