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目的研究口服抗肿瘤药CA4P后,CA4在大鼠体内的药物动力学规律。方法HPLC检测方法,以Aichrom Bond-1C18(150mm×4.6mm,5μm)为色谱柱,检测波长305nm,流动相为0.05mol·L-1磷酸二氢钾-甲醇-乙腈(50∶10∶40);流速1.0mL·min-1,测定口服20、50、90mg·kg-1CA4P后,大鼠血浆中CA4的药物浓度。结果CA4血浆浓度0.0155～7.7500μg·mL-1的线性关系良好(r=0.9999),最低检测浓度为7.75ng·mL-1,最低检测量0.3875ng;日内RSD为2.55%～4.87%;日间RSD为5.06%～8.28%;方法回收率为94.91%～99.85%;口服CA4P后,CA4在大鼠体内的动力学过程符合二室模型,t1/2β分别为48.74、96.37min,CL分别为7.542、9.477L·min-1·kg-1,Vd分别为131.39、450.19L·kg-1,AUC0-t分别为4.999、7.771mg·L·min-1,生物利用度分别为0.54%、0.47%。结论口服CA4P后,水解产生的难溶性CA4在体内吸收极弱,不宜直接口服给药。
Objective To study the pharmacokinetics of CA4 in rats after oral anticancer drug CA4P. Methods The HPLC method was as follows: Aichrom Bond-1C18 (150mm × 4.6mm, 5μm) was used as the chromatographic column. The detection wavelength was 305nm and the mobile phase was 0.05mol·L -1 potassium dihydrogen phosphate-methanol- ; The flow rate of 1.0mL · min-1, measured after oral administration of 20,50,90 mg · kg-1CA4P, the concentration of CA4 in rat plasma. Results The linear range of CA15 plasma concentration was 0.0155-7.7500μg · mL-1 (r = 0.9999), the lowest concentration was 7.75ng · mL-1 and the lowest was 0.3875ng. The intra-day RSD was 2.55% -4.87% RSD ranged from 5.06% to 8.28%. The recoveries were 94.91% to 99.85%. After oral administration of CA4P, the kinetics of CA4 in rats was in accordance with the two-compartment model with t1 / 2β of 48.74 and 96.37 min, CL of 7.542 , 9.477L · min-1 · kg-1, Vd were 131.39 and 450.19L · kg-1, AUC0-t were 4.999,7.771mg · L · min-1, bioavailability were 0.54%, 0.47% . Conclusion After oral administration of CA4P, the insoluble CA4 produced by hydrolysis is extremely weak in the body and should not be administered orally directly.