中药黄药子对大鼠阿霉素药物动力学的影响

Effect of Dioscora bulbiferea L. rhiizoma , a traditional Chinese medicine on pharmacokinetics of doxorubicin

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 .

AIM: To investigate the effect of Dioscora bulbiferea L. rhiizoma (DBR), a traditional Chinese medicine for cancer, on pharmacokinetics of doxorubicin (Dox) in rats. METHODS: High performance liquid chromatography (HPLC) method measuring Dox concentration in plasma and urine was established to measure and compare the pharmacokinetic parameters and plasma protein binding rate between test group and control group. RESULTS: The terminal elimination rate constant [(β, (0 44±0 23), (2 48±0 43)h -1 ], transfer rate constant between peripheral and central compartment [ k 21 , (0 580±0 243), (3 10±0 33)h -1 ], mean clearance rate [ Cl, (2 42±0 49), (1 66±0 48)L/h], apparent distribution volume [ V , (0 14±0 05), (0 08±0 04)L] and steady apparent distribution volume [ V ss , ( 2 09± 1 47), (0 23±0 15)L] were significantly difference between control group and test group ( P <0 05). However, The area under the plasma concentration time curve [ AUC , (2 57±0 62), (3 88±1 31)μg·h/ml], distribution rate constant [α, (25 54±7 85), (26 34±2 55 h -1 ], central compartment elimination rate constant [ k 10 , (19 20±8 30), (21 0±3 20)h -1 ], transfer rate constant between central and peripheral compartment [ k 12 , (6 19±1 39), (4 66±2 56)h -1 ] were no significant difference ( P >0 05) between test group and control group, and the liver function results within 2 groups [control group (20 60±0 86)U, test group (21 76±0 36)U], were also no significant difference ( P >0 05). The plasma protein binding rate of Dox at 0 06、0 60、6 0 μg/ml between test group and control group were (62 54±2 62)%,(64 83±3 84)%, (65 49±2 36)% and (66 54±2 39)%, (69 47±7 00)%, (73 17±1 76)%, respectively. A significant decrease ( P <0 05) of urine recovery (Xu%) unchanged Dox was seen in test group (5 62±0 63)% as compared to that in control group (8 03±0 83)%. The lower limit of detection of Dox in plasma and urine was 0 01 μg/ml by HPLC, and the extract recovery of Dox from plasma and urine was 90 96%-98 25%. The intra day and inter day variabilities for plasma samples at 0 12, 0 80 and 1 40 μg/ml were <6% ( n=5 ). CONCLUSION: The pharmacokinetic interaction between Dox and DBR exists in rat and DBR effects mainly the distribution of Dox in the tissues.