胸腺五肽聚乳酸-羟基乙酸共聚物长效微球在大鼠体内的药动学研究

Pharmacokinetic Study of Thymopentin PLGA Long-acting Microspheres in Rats

目的：研究胸腺五肽（TP5）聚乳酸-羟基乙酸共聚物（PLGA）长效微球（简称“TP5长效微球”）在大鼠体内的药动学特征。方法：取8只大鼠均分为普通注射液组（以TP5计1.5 mg/kg）和长效微球组（以TP5计40 mg/kg）,单剂量肌肉注射相应的异硫氰酸荧光素标记TP5（FITC-TP5）,以酶标仪测定普通注射液组（给药后0、5、10、15、30 min和1、2、4、6、10、24 h）和长效微球组（给药后0、0.5、1、2、4、10、24 h和4、7、14、21、28、35、42、49 d）大鼠体内FITC-TP5的荧光强度,计算血药浓度,采用DAS 2.0软件计算药动学参数和长效微球的累积释药情况。结果：普通注射液组和长效微球组大鼠体内FITC-TP5的药动学参数分别为t1/2z：0.031、9.292d,tmax：0.021、0.042 d,MRT0-∞：0.064、11.351 d,cmax：0.706、0.909 mg/L,AUC0-∞：0.078、2.554 mg·d/L;与普通注射液相比,长效微球中FITC-TP5的t1/2延长了299.7倍、MRT延长了177.3倍,缓释特征符合Higuchi方程,相对生物利用度为123%。结论：TP5长效微球可在大鼠体内缓慢释放,释药周期达42~49d。

OBJECTIVE： To study the in vivo pharmaeokinetic characteristics of thymopentin （TPS） PLGA long-acting microspheres （TP5 long-acting microspheres） in rats. METHODS： 8 rats were divided into TP5 injection group （TPS, 1.5 mg/kg） and long-acting microspheres group （TP5, 40 mg/kg）. After TP5 labeled with single intramuscular injection of fluorescein isothiocyahate （FITC）, the fluorescence intensity of FITC-TP5 in rats were determined in TP5 injection group （0, 5, 10, 15, 30 min and 1, 2, 4, 6, 10, 24 h after treatment） and long-acting microspheres group （0, 0.5, 1, 2, 4, 10, 24 h and 4, 7, 14, 21, 28, 35, 42, 49 d after treatment）. Blood concentration was calculated, and pharmacokinetic parameters and accumulative drug release of long-acting microspheres were calculated by using DAS 2.0 software. RESULTS： Pharmacokinetic parameters of TP5 injection group vs. long-acting microspheres group were as follows： tlnz 0.031 d vs. 9.292 d; tmax 0.021 d vs. 0.042 d; MRT0-∞ 0.064 d vs. 11.351 d; cmax 0.706 mg/L vs. 0.909 mg/L; AUC0-∞ 0.078 mg. d/L vs. 2.554 mg. d/L. Compared with TP5 injection group, in long-acting microspheres group, tt/z of FITC-TP5 extended by 299.7 times, and MRT extended by 177.3 times; the sustained re- lease characteristics were in line with Higuchi equation, and relative bioavailability was 123%. CONCLUSIONS： TP5 long-acting microspheres show sustained release characteristics in rats with the release period of 42-49 days.