胰岛素胶囊在Beagle犬体内的药动学和药效学研究

目的研究胰岛素胶囊在Beagle犬体内药动学和药效学特征。方法 4只健康Beagle犬sc重组人胰岛素注射液以及po和内窥镜给予胰岛素胶囊,不同时间经静脉采集血浆标本,同步测定血糖水平,采用放射免疫分析法检测血药浓度。结果 4只Beagle犬自身交叉分别sc胰岛素注射液和po胰岛素胶囊或内窥镜给予内容物后,以血浆外源性胰岛素浓度计算得到的主要药动学参数,t_(1/2)分别为(0.986±0.185)、(0.649±0.508)、(0.518±0.187)h;C_(max)分别为(102.0±45.7)、(625.0±360.0)、(453.0±636.0)μU/mL;tmax分别为(0.375±0.224)、(0.750±0.289)、(0.500±0.601)h;AUC_(0-t)分别为(181.0±42.6)、(414.0±246.0)、(423.0±526.0)μU/(mL·h)。胰岛素胶囊po和内窥镜插管给药的相对生物利用度分别为(5.41±2.26)%、(8.31±9.94)%。po和内窥镜这两种途径的胰岛素胶囊在0.5~1.0 h浓度达到最大,然后在血液中的外源性胰岛素浓度逐渐降低,直至检测不到,波动范围较大;t_(1/2)基本为0.5 h左右,作用时间较短;血糖值降低的维持时间较短,回升速度快,且血糖值的波动较大。结论通过直接po和内窥镜给予胰岛素胶囊内容物,与sc短效胰岛素的结果相比,尽管口服胰岛素胶囊在Beagle犬体内吸收和消除均比较快,动物的个体差异影响较明显;但是仍然具有降糖的作用。

Pharmacokinetics and pharmacodynamics of Insulin Capsules in Beagle dogs

Objective To study the pharmacokinetic and pharmacodynamic characteristics of Insulin Capsules in Beagle dogs. Methods Four healthy Beagle dogs were given subcutaneous injection of Recombinant Human Insulin Injection and oral and endoscopic administration of Insulin Capsules. Plasma samples were collected at different time points and blood glucose levels were measured synchronously. Blood concentration of serum was determined by radioimmunoassay (RIA) method. Results After 4 Beagle dogs themselves crossed were given insulin preparations, t1/2 were (0.986 ± 0.185), (0.649 ± 0.508), and (0.518 ± 0.187) h, the Cmax was (102.0 ± 45.7), (625.0 ±360.0 ), and (453.0 ± 636.0) μU/mL, tmax were (0.375 ± 0.224), (0.750 ± 0.289), and (0.500 ± 0.601) h, AUC0-t was (181.0 ± 42.6), (414.0 ± 246.0), and (423.0 ± 526.0) μU/(mL·h), F of oral and endoscopic administration of Insulin Capsules were (5.41 ± 2.26)% and (8.31 ± 9.94)%, respectively. Insulin concentration of oral and endoscopic administration of Insulin Capsules reached the maximum during 0.5 — 1 h, then the exogenous insulin concentration in the blood gradually decreased until undetectable and with larger range. T1/2 was about 0.5 h with short response time. The maintenance time of blood glucose value was shorter, the recovery rate was faster, and the fluctuation of blood sugar value was larger. Conclusion Compared with subcutaneous injection of Recombinant Human Insulin Injection, Absorption and elimination of insulin in Beagle dogs by oral and endoscopic administration of Insulin Capsules are faster. and the individual difference of animals are more obvious, but there are still has hypoglycemic effect.