复方苦参注射液对大鼠体内多西他赛药物代谢动力学的影响
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摘要
目的:建立HPLC法测定大鼠血浆药物浓度,探讨不同剂量复方苦参注射液在大鼠体内对多西他赛多次给药后药物代谢动力学的影响。方法:将24只SD大鼠随机分为高、中、低剂量组和对照组,每组6只,大鼠尾静脉注射分别给予2倍临床等效量(3.6 m L/kg)、临床等效量(1.8 m L/kg)、1/2倍临床等效量(0.9 m L/kg)的复方苦参注射液和0.9%氯化钠注射液,连续给药7 d,第7天给予复方苦参注射液或0.9%氯化钠注射液5 min后,注射多西他赛15 mg/kg,按时间点采集血样处理并检测分析,计算药物代谢动力学参数。结果:多次给药后高剂量组、中剂量组AUC、Cmax均低于对照组(P<0.05),低剂量组与对照组差异无统计学意义(P>0.05)。结论:复方苦参注射液联合使用多西他赛后血药浓度有所降低,对多西他赛的抑制作用具有剂量依赖性,可为临床用药提供一定参考。
Objective: To develop a high performance liquid chromatography( HPLC) method for the determination of docetaxol concentration,and investigate the effects of different dosages of compound Kushen injection on the pharmacokinetics of multiple-dose docetaxol in rats. Methods: Twenty-four SD rats were randomly divided into the high-dose,medium-dose,low-dose and control groups( 6 rats each group). The high-dose,medium-dose,low-dose and control groups were injected with 2 times clinical equivalent compound Kushen injection( 3. 6 m L/kg),clinical equivalent compound Kushen injection( 1. 8 m L/kg),1/2 clinical equivalent compound Kushen injection( 0. 9 m L/kg) and 0. 9% normal saline solution by caudal vein for 7 days,respectively,and all rats were injected with 15 mg/kg of docetaxol after 5 min of administration on the seventh day. The blood samples in four groups at different time-points were analyzed,and the pharmacokinetic parameters were calculated. Results: After multiple-dose,the AUC and Cmaxin high-dose and medium-dose groups were lower than those in control group( P < 0. 05),and the difference of which between low-dose group and control group was not statistically significant( P > 0. 05). Conclusions: The compound Kushen injection can reduce the blood concentration of docetaxol,there is a dose-dependent relationship between compound Kushen injection and docetaxel,which can provide a reference in clinical medication.
Objective: To develop a high performance liquid chromatography( HPLC) method for the determination of docetaxol concentration,and investigate the effects of different dosages of compound Kushen injection on the pharmacokinetics of multiple-dose docetaxol in rats. Methods: Twenty-four SD rats were randomly divided into the high-dose,medium-dose,low-dose and control groups( 6 rats each group). The high-dose,medium-dose,low-dose and control groups were injected with 2 times clinical equivalent compound Kushen injection( 3. 6 m L/kg),clinical equivalent compound Kushen injection( 1. 8 m L/kg),1/2 clinical equivalent compound Kushen injection( 0. 9 m L/kg) and 0. 9% normal saline solution by caudal vein for 7 days,respectively,and all rats were injected with 15 mg/kg of docetaxol after 5 min of administration on the seventh day. The blood samples in four groups at different time-points were analyzed,and the pharmacokinetic parameters were calculated. Results: After multiple-dose,the AUC and Cmaxin high-dose and medium-dose groups were lower than those in control group( P < 0. 05),and the difference of which between low-dose group and control group was not statistically significant( P > 0. 05). Conclusions: The compound Kushen injection can reduce the blood concentration of docetaxol,there is a dose-dependent relationship between compound Kushen injection and docetaxel,which can provide a reference in clinical medication.
引文
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[12]王栋海,杨光丽,邹伟伟,等.注射用多西他赛脂质体的制备及其体内外评价[J].中国新药杂志,2011,20(1):24.
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[14]林巧平,郭仁平,王青松,等.注射用多西他赛脂质体的制备、体外释放及细胞毒作用[J].中国药科大学学报,2008,39(5):417.
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[16]林高通,徐涛,罗俊,等.复方苦参注射液在大鼠体内对伊马替尼药动学的影响[J].中国现代应用药学,2016,33(12):1547.
[17]SHI G,ZHANG L.Effects on type 2 diabetes complicated with pulmonary tuberculosis:regiment of insulin,isoniazid,rifampicin,pyrazinamide and ethambutol versus the regiment plus Qi-boosting and Yin-nourishing decoction of Traditional Chinese Medicine[J].J Tradit Chin Med,2015,35(3):260.
[2]黄思夏,范文斌,刘鹏,等.复方苦参注射液联合铂类化疗药物治疗中晚期胃癌的Meta分析[J].中国中药杂志,2011,36(22):3198.
[3]鲍娇琳,陆金健,陈修平,等.苦参碱与氧化苦参碱抗肿瘤作用及其机制的研究进展[J].中药新药与临床药理,2012,23(3):369.
[4]XIAO Y,HONGBO LI,JIANG Z,et al.The effect of matrine on bone marrow and cell apoptosis of patients radiated by192Ir[J].Medicinal Plant,2013,4(4):32.
[5]ROUHI-BOROUJENI H,ROUHI-BOROUJENI H,HEIDARIAN E,et al.Herbs with anti-lipid effects and their interactions with statins as a chemical anti-hyperlipidemia group drugs:A systematic review[J].ARYA Atheroscler,2015,11(4):244.
[6]王茂林,宣玲,唐碧,等.环孢素A对心房颤动大鼠心房有效不应期及血清中MMP-2、TIMP-2水平的影响[J].蚌埠医学院学报,2014,39(2):141.
[7]MOHAMMADIAN J,SABZICHI M,MOLAVI O,et al.Combined treatment with stattic and docetaxel alters the Bax/Bcl-2 gene expression ratio in human prostate cancer cells[J].Asian Pac J Cancer Prev,2016,17(11):5031.
[8]PAGLIARO LC,ZURITA AJ,ARAUJO JC,et al.Presurgical docetaxel(Doc)and androgen deprivation therapy(ADT)in lymph node-positive prostate cancer(PCa)[J].J Clin Oncol,2011,29(15 suppl):4619.
[9]方红明,蒋国军,万宇,等.复方苦参注射液联合多西他赛每周方案治疗老年晚期非小细胞肺癌33例临床观察[J].中医杂志,2012,53(9):764.
[10]贾海清,王晓斌.复方苦参注射液联合多西他赛和奈达铂治疗中晚期宫颈癌的临床研究[J].现代药物与临床,2016,31(3):363.
[11]谢玲玲,罗卓雅,洪建文,等.HPLC法测定注射用多西他赛纳米粒中溶血磷脂酰胆碱含量[J].药物分析杂志,2014,34(5):874.
[12]王栋海,杨光丽,邹伟伟,等.注射用多西他赛脂质体的制备及其体内外评价[J].中国新药杂志,2011,20(1):24.
[13]刘芳,王淑君.多西他赛纳米乳注射液的制备与药代动力学研究[J].亚太传统医药,2013,9(3):38.
[14]林巧平,郭仁平,王青松,等.注射用多西他赛脂质体的制备、体外释放及细胞毒作用[J].中国药科大学学报,2008,39(5):417.
[15]LIU D,LIANG XC.New developments in the pharmacodynamics and pharmacokinetics of combination of Chinese medicine and Western medicine[J].Chin J Integr Med,2017,23(4):312.
[16]林高通,徐涛,罗俊,等.复方苦参注射液在大鼠体内对伊马替尼药动学的影响[J].中国现代应用药学,2016,33(12):1547.
[17]SHI G,ZHANG L.Effects on type 2 diabetes complicated with pulmonary tuberculosis:regiment of insulin,isoniazid,rifampicin,pyrazinamide and ethambutol versus the regiment plus Qi-boosting and Yin-nourishing decoction of Traditional Chinese Medicine[J].J Tradit Chin Med,2015,35(3):260.