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目的 :观察黄药子 (DBR)作为抗癌药对大鼠阿霉素 (Dox)药物动力学的影响。方法 :建立测定血浆及尿中 Dox浓度的HPL C法 ,比较试验组及对照组药物动力学参数及血浆蛋白结合率。结果 :对照组 (仅给予 Dox)与试验组 (给予 DBR及 Dox)之间的末端除速度常数 [β,(0 .44± 0 .2 3)、(2 .48± 0 .43) h- 1 ],周边室向中央室转运速度常数 [k2 1 ,(0 .5 80± 0 .2 43)、(3.10±0 .33) h- 1 ],清除率 [Cl,(2 .42± 0 .49)、(1.6 6± 0 .48) L/ h],表观分布体积 [V,(0 .14± 0 .0 5 )、(0 .0 8± 0 .0 4) L]及稳态表观分布体积 [Vss,(2 .0 9± 1.47)、(0 .2 3± 0 .15 ) L],存在显著性差异 (P<0 .0 5 ) ;相反 ,血药浓度 -时间曲线下面积 [AUC,(2 .5 7±0 .6 2 )、(3.88± 1.31) μg· h/ ml],分布速度常数 [α,(2 5 .5 4± 7.85 )、(2 6 .34± 2 .5 5 ) h- 1 ],中央室消除速度常数 [k1 0 ,(19.2 0±8.30 )、(2 1.0± 3.2 0 ) h- 1 ],中央室向周边室转运速度常数 [k1 2 ,(6 .19± 1.39)、(4 .6 6± 2 .5 6 ) h- 1 ],没有显著性差异 (P>0 .0 5 ) ,肝功能的结果也显示两组之间 GPT水平无显著差异 (n=15 ,P>0 .0 5 )。对照组及试验组 Dox的浓度为 0 .0 6、0 .6 0、6 .0 μg/ml 的血浆蛋白结合率分别为 (6 2 .5 4± 2 .6
Objective : To observe the effect of DBR as an anticancer drug on the pharmacokinetics of doxorubicin (Dox) in rats. Methods : HPL C method was established for the determination of Dox concentration in plasma and urine. The pharmacokinetic parameters and plasma protein binding of the test and control groups were compared. RESULTS: The terminal velocity constants between the control group (Dox only) and the test group (DBR and Dox) were [β, (0.44 ± 0.23), (2.48 ± 0.43) h- 1 ], Peripheral chamber velocity constants [k2 1 , (0.50 ± 0.23), (3.10 ± 0.33) h - 1], clearance [Cl, (2 .42 ± 0) .49), (1.6 6 ± 0 .48) L/h], apparent volume of distribution [V, (0.14 ± 0.55), (0.08 ± 0.04) L] and stability Apparent apparent volume of distribution [Vss,(2.09±1.47),(0.23±0.15)L], with significant difference (P<0.05); on the contrary, plasma concentration-time The area under the curve [AUC, (2.77 ± 0.62), (3.88 ± 1.31) μg·h/ml], distribution rate constant [α, (2 5 .5 4 ± 7.85), (2 6 . 34±2.55) h-1, the central chamber eliminates velocity constants [k1 0, (19.2 0±8.30), (2 1.0± 3.2 0) h-1], and the transfer rate constant from the central chamber to the peripheral chamber [k1 2 , (6 .19± 1.39), (4.66 + 2.5.6) h - 1 ], there was no significant difference (P > 0.05), and liver function results also showed GPT between the two groups There was no significant difference in levels (n=15, P>0.05). The plasma protein binding rates of Dox concentrations in the control and experimental groups were 0.66, 0.60, and 6.0 μg/ml, respectively (6 2 .5 4± 2 .6).