摘要
目的 用Cocktail探针药物法，研究血栓通注射液对大鼠肝细胞细胞色素P450（CYP450）的影响。方法 分别以茶碱、氯唑沙宗和咪哒唑仑作为CYP1A2，CYP2E1及CYP3A4的探针药，将大鼠随机分为低剂量和高剂量两组，每日尾静脉注射血栓通注射液，采用高效液相色谱法测定连续使用血栓通注射液前后大鼠血浆中相应的探针药物的浓度及其药动学参数。结果 连续注射14 d后，与用药前比较，茶碱、氨苯砜的血药浓度及其药动学参数未见显著性改变；但低剂量组和高剂量组中氯唑沙宗的AUC0-t减少，ρmax明显降低，CL/F显著增加，t1/2和Vd/F变化不明显。高剂量组中tmax有所降低(P<0.05)。结论 连续注射血栓通注射液14 d后，对CYP2E1酶活性有显著诱导作用，而对CYP3A4、CYP1A2酶活性无影响。
Abstract
OBJECTIVE To evaluate the effects of Xueshuantong Injection on P450 activities by Cocktail probe drugs in rats.METHODS Three probe drugs (theophylline， dapsone， chlorzoxazone) were simultaneously given to rats after middle and high dosing of Xueshuantong injection. The plasma concentrations of the three probes were measured by HPLC and their corresponding pharmacokinetic parameters were calculated. RESULTS There were no differences on theophylline and dapsone plasma concentrations and the corresponding pharmacokinetic parameters in rats between before and after Xueshuantong injection administration for 14 d. But AUC0-t and the concentration of chlorzoxazone were decreased significantly (P< 0.05) and the CL/F was increased in rats after Xueshuantong Injection for 14 consecutive days. No influences were observed on t1/2 and Vd/F.CONCLUSION Xueshuantong injection can induce CYP2E1 activity significantly， but it shows no effect on CYP3A4 and CYP1A2.
关键词
Cocktail /
探针药物 /
血栓通注射液 /
细胞色素P450
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Key words
Cocktail /
probe /
Xueshuantong injection /
CYP450
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刘史佳 居文政 陈为烤 许黎君 熊宁宁 谈恒山.
血栓通注射液对大鼠体内细胞色素P450酶活性的影响[J]. 中国药学杂志, 2010, 45(2): 115-118
LIU Shi-ji;JU Wen-zheng;CHEN Wei-ko;XU Li-jun;XIONG Ning-ning;TN Heng-shn.
Influence of Xueshuantong Injection on P450 Activities Using a Cocktail Method[J]. Chinese Pharmaceutical Journal, 2010, 45(2): 115-118
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参考文献
［1］ CHEN X Q， JIN Y Y.New Edition Materia Medica（新编药物学）［M］. 15th ed. Beijing： People′s Medical Publishing House， 2003： 732.
［2］ FU P， LIU Z Y. Determination of the effecient elements of Xuesai-tong for injection， Xueshuantong injection and Xuemaitong for injection by fingerprint［J］. West China Pharm Sci（华西药学杂志），2007， 22(1)： 76-78.
［3］ LIU Y，JIAO J J，LOU J S. Progress of“Cocktail”probe substrates approaches［J］.Chin J Clin Pharmacol Ther（中国药理学与治疗学杂志），2006，11 (11)：1225-1229.
［4］ WRIGHTON S A， VANDEN-BRANDEN M， RING B J.The human drug metabolizing cytochromes P450［J］. J Pharmacokinet Biopharm， 1996， 24(5)：461-473.
［5］ DU Y， ZHU R H， SU F H，et al. Effect of oleanolic acid on CYP1A2， CYP2E1 and CYP3A4 activity in healthy subjects［J］. Chin Pharm J（中国药学杂志）， 2008， 43(4)：300-303.
［6］ XIAO Y J， JIANG Z Z， YAO J C， et al. Investigation of picroside II′s impacts on the P450 activities using a cocktail method［J］. Chin J Nat Med（中国天然药物）， 2008, 6 (4)：292-297.
［7］ YAN S L，HU J P，XU Y X， et al. Simultaneous evaluation of activity of hepatic CYP450 following administration of Fisch Fructus Forsythiae Cocktail probe drugs［J］. Chin Pharm J（中国药学杂志），2003， 38(10)：761-763.
［8］ HU J P， YAN S L， TANG J C， et al. Simultaneous evaluation of effect of rhizoma Curcumae Longae on hepatic CYP450 by cocktail probe drugs［J］. J Cap Univ Med Sci(首都医科大学学报)， 2004， 25(4)：427-430.
［9］ SHI J， CHEN A J， ZHANG F， et al. Effects of traditional Chinese medicine Panax notoginoside and Tetramethylpyrazine on cytochrome P450 subtype enzymes［J］. Chin J Integr Tradit West Med Intens Crit Care (中国中西医结合急救杂志)， 2008， 15(6)：342-345.
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