银杏叶片长期给药后对大鼠灌服氯沙坦的药代动力学影响

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (12): 1326-1331.

银杏叶片长期给药后对大鼠灌服氯沙坦的药代动力学影响

潘沛¹, 王世明¹, 郭竹英², 原永芳¹

¹上海交通大学医学院附属第三人民医院药剂科, ²实验中心,上海 201900

收稿日期:2011-08-04 修回日期:2011-11-16 出版日期:2011-12-26 发布日期:2012-01-07
作者简介:潘沛,女,硕士在读,药师,研究方向:临床药学。Tel: 021-56691101-6322 E-mail: ganlin149@hotmail.com原永芳,女,硕士,主任药师,研究方向:临床药学。
基金资助:
上海市卫生局科研项目(2010228);上海医院药学科研基金(2010-YY-02-20);上海交通大学医学院药学科研基金(JYY0915)

Effect of Ginkgo biloba talbes on the pharmacokinetics of intragastrically administered losartan in rats

PAN Pei¹, WANG Shi-ming¹, GUO Zhu-ying², YUAN Yong-fang¹

¹Department of Pharmacy, No.3 People's Hospital Affiliated to Shanghai Jiao Tong University of Medicine, Shanghai 201900, China;
²No.3 People's Hospital Affiliated to Shanghai Jiao Tong University of Medicine Experimental Center,Shanghai 201900, China

Received:2011-08-04 Revised:2011-11-16 Online:2011-12-26 Published:2012-01-07

摘要/Abstract

摘要： 目的: 研究银杏叶提取物(GBE)制剂银杏叶片长期给药后对大鼠灌服氯沙坦(Los)的药代动力学影响。方法: SD大鼠随机分为Los单用组,GBE+Los联合用药组。试验第1天起,联合用药组大鼠灌胃给予GBE 100 mg/kg,共 14 d。单用组大鼠灌胃给予等量纯净水。第15天,单用药组大鼠灌胃给予Los 10 mg/kg,GBE+Los联合给药组大鼠同时灌胃给予GBE 100 mg/kg 和Los 10 mg/kg。于Los给药后0.5、1、2、3、4、6、8、10、12、24 h 从大鼠眼眦静脉丛取血。HPLC法测定血浆中Los及其活性代谢产物EXP3174的浓度,计算其主要药代动力学参数,并进行统计学分析。结果: 合用GBE后,Los的各药代动力学参数差异无统计学意义。EXP3174的t_max显著缩短(P<0.05),C_max、AUC_0-8和AUC_0-∞显著增加(P<0.01),CL显著降低(P<0.05),t_1/2、MRT变化无统计学差异。结论: GBE能够影响EXP3174的体内代谢,但对Los的药代动力学过程影响没有统计学意义。

关键词: 银杏叶提取物, 氯沙坦, 细胞色素P450, 药代动力学

Abstract: AIM: To investigate the possible effect of ginkgo biloba tablets which were prepared by Ginkgo biloba extracts (GBE) on the pharmacokinetics of losartan by intragastrically administering in rats.METHODS: SD rats were randomly divided into two groups (losartan group and GBE+losartan group).Rats in GBE+losartan group were administered with GBE 100 mg/kg from day 1 to 14. On day 15, Rats in the losatan group were administered with losartan 10 mg/kg, and Rats in the GBE+losartan group were added with GBE 100 mg/kg.Blood samples were collected from the angulus oculi veins at 0.5,1,2,3,4,6,8,10,12,24 h.The blood plasma concentration of losartan and EXP3174 were determined by HPLC.Main pharmacokinetic parameters were calculated and compared by statistical analysis.RESULTS: After co-administrating with GBE, there were no significantly different pharmacokinetic parameters of losartan were found.However, the t_max of EXP3174 was markedly decreased (P<0.05). The C_max,AUC_{0-8 h}, AUC_0-∞ of EXP3174 were significantly increase (P<0.01). And the CL of EXP3174 was markedly decreased (P<0.01).There was no significantly changed of t_1/2 and MRT about EXP3174.CONCLUSION: GBE can affect the metabolism of EXP3174, which were no significantly different on the pharmacokinetics of losartan.

Key words: Ginkgo biloba extracts, Losartan, CYP, Pharmacokinetics

中图分类号:

R969.1

潘沛, 王世明, 郭竹英, 原永芳. 银杏叶片长期给药后对大鼠灌服氯沙坦的药代动力学影响[J]. 中国临床药理学与治疗学, 2011, 16(12): 1326-1331.

PAN Pei, WANG Shi-ming, GUO Zhu-ying, YUAN Yong-fang. Effect of Ginkgo biloba talbes on the pharmacokinetics of intragastrically administered losartan in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1326-1331.

参考文献

[1] Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan [J]. Clin Pharmacokinet, 2005, 44(8):797-814.
[2] Bailey DG, Dresser GK. Interactions between grapefruit juice and cardiovascular drugs [J]. Am J Cardiovasc Drugs,2004, 4(5):281-297.
[3] Mahadevan S, Park Y. Multifaceted therapeutic benefits of Ginkgo biloba L: chemistry, efficacy, safety, and uses [J]. J Food Sic,2008, 73(1): R14-19.
[4] 赵丰戎, 赵丰文, 孙连军. 银杏叶胶囊合并综合康复训练治疗慢性精神分裂症临床观察[J]. 中国临床药理学与治疗学, 2010, 15(5): 565-569.
[5] Zhou S, Gao Y, Jiang W, et al. Interactions of herbs with cytochrome P450 [J]. Drug Metab Rev, 2003, 35(1): 35-98.
[6] Hellum BH, Nilsen OG. In vitro inhibiton of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products [J]. Basic Clin Pharmacol Toxicol,2008, 102(5): 466-475.
[7] Soldner A, Spahn-Langguth H, Mutschler E. HPLC assays to simultaneously determine the angiotensin-AT1 antagonist losartan as well as its main and active metabolite EXP3174 in biological material of humans and rats [J]. J Pharm Biomed Anal, 1998, 16(5):863-873.
[8] 韦阳, 黄慧芳, 邵庆翔,等. 国产氯沙坦钾片的生物等效性研究[J]. 中国临床药理学杂志,2000, 16(2): 106-110.
[9] 李烈权. 高效液相色谱荧光法测定人血浆氯沙坦浓度[J]. 中国民康医学,2009, 20(15): 1738-1740.
[10] 孙鲁宁, 刘园园, 赵燕荣. HPLC-MS法同时测定人血浆中氯沙坦及其代谢物EXP-3174[J]. 药学与临床研究,2009, 17(2): 115-119.
[11] Lo MW, Goldberg MR, Mccrea JB, et al. Pharmacokinetics of losartan, an angiotensin II receptor antagonist and it's active metabolite EXP3174 in humans [J]. Clinical Pharmacol Therapy, 1995, 58(6): 641-539.
[12] Li L, Stanton JD, Tolson AH, et al. Bioactive terpenoids and flavonoids from Ginkgo biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor-mediated pathways [J]. Pharm Res, 2009, 26(4):872-882.
[13] 邓颖, 赵立子, 毕惠嫦, 等. 银杏叶提取物及其萜类单体对孕烷X受体介导CYP3A4转录的调节作用[J].中药新药与临床药理, 2009, 20(3):234-237.

[1]	李士旭, 李林运, 王新, 李轲, 卞华. 银杏叶提取物通过miR-145/FOXO1轴对实验性肾功能衰竭大鼠肾脏损伤的影响[J]. 中国临床药理学与治疗学, 2023, 28(7): 728-735.
[2]	何雪茹, 李颖, 马银玲, 付裕豪, 荀雪姣, 董占军. 索拉非尼和达格列净在大鼠体中药代动力学相互作用研究[J]. 中国临床药理学与治疗学, 2023, 28(5): 498-507.
[3]	朱丽, 魏兵, 廖世峨, 张超, 郑晓宇, 刘亚军. 药物代谢酶细胞色素P450单核苷酸多态性影响哮喘儿童吸入皮质醇激素疗效研究[J]. 中国临床药理学与治疗学, 2023, 28(5): 536-543.
[4]	李梦雪, 何杰, 余霞霞, 胡琳璘, 邵华. 利妥昔单抗群体药代动力学研究进展[J]. 中国临床药理学与治疗学, 2023, 28(4): 468-474.
[5]	周佳婷, 张玄, 谢子兰, 李智. 肠道菌群与左旋甲状腺素：相互影响与临床意义[J]. 中国临床药理学与治疗学, 2023, 28(11): 1307-1314.
[6]	吴莉莉, 梁至, 黄思咏, 王妍. 肾功能亢进对感染性心内膜炎患者万古霉素药动学的影响及有效性与安全性研究[J]. 中国临床药理学与治疗学, 2023, 28(10): 1139-1145.
[7]	徐涛, 朱素燕, 邱相君, 徐萍. 肾功能不全患者人群中替考拉宁群体药代动力学模型的建立与验证[J]. 中国临床药理学与治疗学, 2022, 27(9): 977-983.
[8]	马申, 刘玉硕, 唐辉, 陈文斌, 高聆. 改善非酒精性脂肪性肝病药物的药代动力学及其临床意义[J]. 中国临床药理学与治疗学, 2022, 27(8): 908-918.
[9]	戴静怡, 王晶晶, 张菁, 郁继诚, 李南洋, 黄志伟. 吸入性甲氧氟烷的临床应用及研究进展[J]. 中国临床药理学与治疗学, 2022, 27(7): 808-813.
[10]	潘淑, 吴义金, 张洒洒, 王启海, 罗婷婷, 殷勤. 基于OAT3介导的MTX治疗佐剂诱导性关节炎大鼠的药动学研究[J]. 中国临床药理学与治疗学, 2022, 27(5): 516-525.
[11]	吴娟, 王志强, 周仁鹏, 杨晶晶, 秦慧玲, 张茜, 鲁超, 胡伟. 甲苯磺酸索拉非尼片在中国健康受试者的生物等效性研究[J]. 中国临床药理学与治疗学, 2022, 27(3): 281-286.
[12]	史革鑫, 崇锐, 贺坤, 吴海棠, 周宇, 顿中军, 温清, 张继国, 张荣. 吗替麦考酚酯胶囊在中国健康男性受试者空腹及餐后状态下的完全重复交叉设计的生物等效性研究[J]. 中国临床药理学与治疗学, 2022, 27(11): 1255-1263.
[13]	郭璐, 钟振东, 韩奕岑, 石毅, 杨勇, 边原, 刘晓姝, 张静, 郎琴, 钟甜. 不同给药方式在大鼠内对利巴韦林的药代动力学和组织分布的影响[J]. 中国临床药理学与治疗学, 2022, 27(1): 25-32.
[14]	林良沫, 符祥俊, 钟莉莉, 王和芳, 吴琼诗, 肖坚. 中性粒细胞缺乏患者万古霉素群体药代动力学模型的建立[J]. 中国临床药理学与治疗学, 2021, 26(9): 1014-1022.
[15]	付淑军, 黄芳华, 顾景凯, 吴伟, 孙涛, 王庆利. 纳米药物非临床药代动力学的研究策略及关注要点[J]. 中国临床药理学与治疗学, 2021, 26(8): 842-850.