环维黄杨星D磷脂复合物药代动力学评价

目的 建立柱前衍生化HPLC/FLD法测定SD大鼠血浆中环维黄杨星D(CB)的含量,考察SD大鼠口服灌胃给予CB磷脂复合物(CBPC)药代动力学特征。 方法 以溶剂挥发法制备CBPC。采用星点设计优化制备工艺,以磷脂/CB、主药浓度作为考察指标,以复合率为评价指标。雄性SD大鼠12只,随机分为2组,口服灌胃给予CBPC和CB (60 mg/kg,以CB计)后,分别在15 min、30 min、1、2、3、4、5、6、8、12、24 h等时间点于大鼠眼底静脉丛取血,以HPLC/FLD法测定血浆中CB的浓度。采用C18色谱柱(250 mm × 4.6 mm,5 μm),以甲醇-水(85∶15)为流动相,流速1.0 mL·min-1,荧光检测激发波长231 nm,发射波长385 nm,柱温25℃。 结果 CBPC和CB的主要药动学参数如下:AUC0-t为(1 703.81±549.38) μg·h·L-1和(619.93±75.67) μg·h·L-1;Tmax为(6.00±0) h和(4.33±0) h;Cmax为(82.32±9.55) μg·L-1和(69.27±8.66) μg·L-1。CBPC的相对生物利用度为274.84%。 结论 磷脂复合物提高了CB的大鼠口服生物利用度。
Objective To develop a pre-column derivatization HPLC/FLD method for determining the content of cyclovirobuxine D (CB) in rat plasma, and to evaluate the pharmacokinetics of cyclovirobuxine D phospholipid complex (CBPC) and CB in SD rats by oral administration. Methods The solvent evaporation method was used to prepare CBPC. The preparation protocol was optimized by central composite design, with the ratio of phospholipid and CB, concentration of principal agent as the independent variables, and with the compound rate as the response variable. Twelve male rats were evenly randomized into two groups with each containing 6 animals. Rats were orally given CBPC and CB (60 mg/kg, with CB count). Blood samples were collected from the retinal venous plexus of SD rats after oral administration of CBPC and CB at 15 min, 30 min, 1, 2, 3, 4, 5, 6, 8, 12 and 24 h time points, and the blood concentrations of CB was determined by HPLC/FLD. The HPLC method employed the C18 column (250 mm × 4.6 mm,5 μm) with a mobile phase of methanol-water (85∶15) at a flow rate of 1.0 mL·min-1. The excitation wavelength was set at 231 nm, emission at wavelength 385 nm, and the column temperature was 25℃. Results The pharmacokinetic parameters of CBPC and CB were calculated as follows: AUC0-t(1 703.81±549.38) μg·h·L-1 and (619.93±75.67) μg·h·L-1, Tmax (6.00±0) h and (4.33±0) h, Cmax(82.32±9.55) μg·L-1 and (69.27±8.66) μg·L-1. The relative bioavailability of CBPC was 274.84%. Conclusion Phospholipid complex can improve the oral bioavailability of CB in rats