目的 研究胰島素膠囊在Beagle犬體內(nèi)藥動(dòng)學(xué)和藥效學(xué)特征。方法 4只健康Beagle犬sc重組人胰島素注射液以及po和內(nèi)窺鏡給予胰島素膠囊，不同時(shí)間經(jīng)靜脈采集血漿標(biāo)本，同步測(cè)定血糖水平，采用放射免疫分析法檢測(cè)血藥濃度。結(jié)果 4只Beagle犬自身交叉分別sc胰島素注射液和po胰島素膠囊或內(nèi)窺鏡給予內(nèi)容物后，以血漿外源性胰島素濃度計(jì)算得到的主要藥動(dòng)學(xué)參數(shù)，t_1/2分別為（0.986±0.185）、（0.649±0.508）、（0.518±0.187）h；C_max分別為（102.0±45.7）、（625.0±360.0）、（453.0±636.0）μU/mL；t_max分別為（0.375±0.224）、（0.750±0.289）、（0.500±0.601）h；AUC_0-t分別為（181.0±42.6）、（414.0±246.0）、（423.0±526.0）μU/（mL·h）。胰島素膠囊po和內(nèi)窺鏡插管給藥的相對(duì)生物利用度分別為（5.41±2.26）%、（8.31±9.94）%。po和內(nèi)窺鏡這兩種途徑的胰島素膠囊在0.5~1.0 h濃度達(dá)到最大，然后在血液中的外源性胰島素濃度逐漸降低，直至檢測(cè)不到，波動(dòng)范圍較大；t_1/2基本為0.5 h左右，作用時(shí)間較短；血糖值降低的維持時(shí)間較短，回升速度快，且血糖值的波動(dòng)較大。結(jié)論 通過(guò)直接po和內(nèi)窺鏡給予胰島素膠囊內(nèi)容物，與sc短效胰島素的結(jié)果相比，盡管口服胰島素膠囊在Beagle犬體內(nèi)吸收和消除均比較快，動(dòng)物的個(gè)體差異影響較明顯；但是仍然具有降糖的作用。

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, t_1/2 were (0.986 ±0.185), (0.649 ±0.508), and (0.518 ±0.187) h, the C_max was (102.0 ±45.7), (625.0 ±360.0), and (453.0 ±636.0) μU/mL, t_max were (0.375 ±0.224), (0.750 ±0.289), and (0.500 ±0.601) h, AUC_0-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. T_1/2 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.

國(guó)家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2016YFE0121400）；國(guó)家科技重大專項(xiàng)重大新藥創(chuàng)制項(xiàng)目（2012ZX09304002）