依托泊苷亚微乳在大鼠体内的药动学研究

Pharmacokinetic study of Etoposide Submicron Emulsion in rats

目的研究依托泊苷亚微乳在大鼠体内的药动学特征,并与依托泊苷注射剂比较。方法大鼠随机分为4组,每组6只,分别尾iv依托泊苷亚微乳2.5、5.0、10.0 mg/kg以及依托泊苷注射剂5 mg/kg,于给药后0.033、0.167、0.333、0.667、1、1.5、2、2.5、3、3.5、4、5、6 h取血。采用HPLC法测定大鼠全血中依托泊苷。结果大鼠iv依托泊苷亚微乳2.5、5、10 mg/kg后的药动学参数分别为t1/2：0.37、0.43、0.46 h;C0：4.72、8.7、15.5 mg/L;AUC0-t：1.57、2.84、6.21 mg·h/L。大鼠尾iv依托泊苷注射剂5 mg/L后的药动学参数分别为：t1/2为0.34 h,C0为7.53 mg/L,AUC0-t为2.63 mg·h/L。依托泊苷亚微乳给药剂量在2.5-10 mg时,t1/2无显著差异,C0、AUC0-t呈剂量相关性,符合线性药动学特点。与注射剂比较,依托泊苷亚微乳的t1/2延长,AUC增大。结论依托泊苷亚微乳的生物利用度有所提高,但半衰期仍然较短。

Objective To study the pharmacokinetic characteristics of Etoposide Submicron Emulsion in rats and compare with Etoposide Injection. Methods Rats were randomly divided into four groups, and each group had six rats. Etoposide Submicron Emulsion at doses of 2.5, 5, and 10 mg/kg and Etoposide Injection at dose of 5 mg/kg were iv administrated. Blood samples were collected at 0.033, 0.167, 0.333, 0.667, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 h. Etoposide in rat whole blood were determined by HPLC method. Results Pharmacokinetic parameters of Etoposide Submicron Emulsion were as follows： t1/2 0.37, 0.43, and 0.46 h, C0 4.72, 8.7, and 15.5 mg/L, AUC0-t 1.57, 2.84, and 6.21 mg·h/L, respectively. And pharmacokinetic parameters of Etoposide Injection were as follows： t1/2 0.34 h, C0 7.53 mg/L, and AUC0-t 2.63 mg·h/L. There was no significant difference of t1/2 for Etoposide Submicron Emulsion at dosage from 2.5 to 10 mg, while C0 and AUC0-t were both dose dependent. Etoposide Submicron Emulsion presented a linear pharmacokinetic behavior. Compared with Etoposide Injection, AUC and t1/2 of Etoposide Submicron Emulsion increased. Conclusion Bioavailability of Etoposide Submicron Emulsion is improved, but half-life is still relatively short.