目的 研究依托泊苷亞微乳在大鼠體內(nèi)的藥動(dòng)學(xué)特征,并與依托泊苷注射劑比較。方法 大鼠隨機(jī)分為4組,每組6只,分別尾iv依托泊苷亞微乳2.5、5.0、10.0 mg/kg以及依托泊苷注射劑5 mg/kg,于給藥后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法測(cè)定大鼠全血中依托泊苷。結(jié)果 大鼠iv依托泊苷亞微乳2.5、5、10 mg/kg后的藥動(dòng)學(xué)參數(shù)分別為t_1/2:0.37、0.43、0.46 h;C₀:4.72、8.7、15.5 mg/L;AUC_0-t:1.57、2.84、6.21 mg·h/L。大鼠尾iv依托泊苷注射劑5 mg/L后的藥動(dòng)學(xué)參數(shù)分別為:t_1/2為0.34 h,C₀為7.53 mg/L,AUC_0-t為2.63 mg·h/L。依托泊苷亞微乳給藥劑量在2.5～10 mg時(shí),t_1/2無(wú)顯著差異,C₀、AUC_0-t呈劑量相關(guān)性,符合線性藥動(dòng)學(xué)特點(diǎn)。與注射劑比較,依托泊苷亞微乳的t_1/2延長(zhǎng),AUC增大。結(jié)論 依托泊苷亞微乳的生物利用度有所提高,但半衰期仍然較短。

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: t_1/2 0.37, 0.43, and 0.46 h, C₀ 4.72, 8.7, and 15.5 mg/L, AUC_0-t 1.57, 2.84, and 6.21 mg·h/L, respectively. And pharmacokinetic parameters of Etoposide Injection were as follows: t_1/2 0.34 h, C₀ 7.53 mg/L, and AUC_0-t 2.63 mg·h/L. There was no significant difference of t_1/2 for Etoposide Submicron Emulsion at dosage from 2.5 to 10 mg, while C₀ and AUC_0-t were both dose dependent. Etoposide Submicron Emulsion presented a linear pharmacokinetic behavior. Compared with Etoposide Injection, AUC and t_1/2 of Etoposide Submicron Emulsion increased. Conclusion Bioavailability of Etoposide Submicron Emulsion is improved, but half-life is still relatively short.