羟喜树碱2种固体分散体在SD大鼠口服吸收生物利用度的比较

Comparison of bioavailability of two kinds of solid dispersion from 10-hydroxycamptothecin in SD rats in vivo

为了提高羟喜树碱的生物利用度,该研究制备了羟喜树碱固体分散体和羟喜树碱磷脂复合物固体分散体,并评价其溶解度、溶出度。SD大鼠分别灌胃给予羟喜树碱固体分散体和羟喜树碱磷脂复合物固体分散体,取血,以喜树碱为内标,HPLC测定羟喜树碱的血药浓度,并计算药动学参数。结果表明羟喜树碱2种固体分散体的C_(max),AUC_(0-t)及AUC_(0-∞)与原料药相比都有显著性提高。羟喜树碱固体分散体的AUC_(0-t)与原料药的AUC_(0-t)相比提高176.87%;而羟喜树碱磷脂复合物固体分散体提高272.59%。因此,羟喜树碱2种固体分散体可显著性提高羟喜树碱的口服吸收生物利用度,但羟喜树碱磷脂复合物固体分散体效果更优。

To improve the bioavailability of 10-hydroxycamptothecin,10-hydroxycamptothecin solid dispersion（ HCPT-SD） and 10-hydroxycamptothecin-phospholipid complex-solid dispersion（ HCPT-PC-SD） were prepared,and their solubility and dissolution rate were evaluated in this study. SD rates were administered intragastrically with HCPT-SD or HCPT-PC-SD respectively,then their blood samples were collected at different time intervals. The concentration of HCPT in blood was detected by HPLC method with camptothecin as internal standard,and then its pharmacokinetic parameters were calculated and obtained. The results showed that the C_（max）,AUC_（0-t） and AUC_（0-∞）of both kinds of solid dispersion of HCPT were significantly increased than those of crude drug. The AUC_（0-t）of HCPT-SD was increased by 176. 87%,and AUC_（0-t）of HCPT-PC-SD was increased by 254. 31% as compared with crude drug. Therefore,the two kinds of solid dispersion of HCPT could significantly enhance the bioavailability of HCPT in SD rates,and the effect of HCPT-PC-SD was more obvious.