当前位置: 首页 » 论文全文
←返回首页
期刊信息:
《药学服务与研究》2018年, 第18卷, 第1期, 第21-25页
标题:
麦考酚酸在大鼠体内的肠肝循环模型
DOI:
10.5428/pcar20180105
作者:
1. 夏琴1(1.上海交通大学医学院附属瑞金医院药剂科 上海 200025 xiaqin_@126.com)
2. 姜慧婷1(1.上海交通大学医学院附属瑞金医院药剂科 上海 200025 )
3. 支建明2(2.上海交通大学医学院生理学教研室 上海 200025 )
4. 陈冰1(1.上海交通大学医学院附属瑞金医院药剂科 上海 200025 chenchenbing@163.com)
摘要:
摘要  目的:研究麦考酚酸(mycophenolic acid,MPA)在大鼠体内的肠肝循环过程。方法:5只雄性SD大鼠静脉注射MPA,收集0~12 h的全血标本,测定MPA浓度。5只雄性大鼠静脉注射给予MPA,收集0~12 h的胆汁标本,测定MPA和7-O-葡糖苷酸麦考酚酸(MPAG)浓度。采用10对雄性SD大鼠建立大鼠肠肝循环模型,测定供体和受体大鼠0~12 h的MPA的血药浓度。结果:大鼠静脉注射MPA 20 mg/kg后 AUC0~12 h为(43.3±20.4) μg·h·ml-1,给药后8 h出现吸收峰。大鼠胆汁实验中,MPA在0~0.33 h、0.33~0.67 h、0.67~1 h、1~1.5 h、1.5~2 h、2~4 h、4~8 h、8~12 h随胆汁排出量为0.078、0.077、0.049、0.062、0.079、0.114、0.120、0.073 mg。胆汁供体组和胆汁受体组大鼠MPA的AUC0~12 h分别是(42.3±27.1)和(4.28±3.05) μg·h·ml-1,胆汁受体组大鼠在接收胆汁后8 h血药浓度达到峰值。结论:约有10%的MPA进行肠肝循环被重吸收,与人体内过程基本一致;大鼠肠肝循环模型中肠肝循环的峰值在给药后的6~8 h。
欢迎阅读《药学服务与研究》!您是该文第 385 位读者!
若需在您的论文中引用此文,请按以下格式著录参考文献:
中文著录格式 夏琴1,姜慧婷1,支建明2,陈冰1. 麦考酚酸在大鼠体内的肠肝循环模型[J]. 药学服务与研究. 2018; 18(1): 21-25.
英文著录格式 XIA Qin1,JIANG HuiTing1,ZHI JianMing2,CHEN Bing1. Enterohepatic circulation of mycophenolic acid in rat models[J]. Pharmaceutical Care and Research / yao xue fu wu yu yan jiu. 2018; 18(1): 21-25.
参考文献:
1. Dong M,Fukuda T,Vinks A A.Optimization of mycophenolic acid therapy using clinical pharmacometrics[J].Drug Metab Pharmacokinet,2014,29(1):4-11.
2. Shaw L M,Nicholls A,Hale M,et al.Therapeutic monitoring of mycophenolic acid: a consensus panel report[J].Clin Biochem,1998,31(5):317-322.
3. Syed M,Srinivas N R.A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids[J].Biomed Chromatogr,2016,30(5):721-748.
4. GENG Fang,JIAO Zheng,DAO YiJun,et al.The association of the UGT1A8,SLCO1B3 and ABCC2/ABCG2 genetic polymorphisms with the pharmacokinetics of mycophenolic acid and its phenolic glucuronide metabolite in Chinese individuals[J].Clin Chim Acta,2012,413(7-8):683-690.
5. Staatz C E,Tett S E.Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients[J].Clin Pharmacokinet,2007,46(1):13-58.
6. Sugioka N,Sasaki T,Kokuhu T,et al.Clinical pharmacokinetics of mycophenolate mofetil in Japanese renal transplant recipients: a retrospective Cohort study in a single center[J].Biol Pharm Bull,2006,29(10):2099-2105.
7. 刘晓雪,黄菁菁,夏琴,等.液-质联用法同时测定人血浆中霉酚酸及其代谢物浓度及其在肝移植患者药动学研究中的应用[J].中国医院药学杂志,2015,35(23):2096-2101.
8. JIAO Zheng,DING JunJie,SHEN Jie,et al.Population pharmacokinetic modelling for enterohepatic circulation of mycophenolic acid in healthy Chinese and the influence of polymorphisms in UGT1A9[J].Br J Clin Pharmacol,2008,65(6):893-907.
9. Dong M,Fukuda T,Cox S,et al.Population pharmacokinetic-pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period[J].Br J Clin Pharmacol,2014,78(5):1102-1112.
10. Cremers S,Schoemaker R,Scholten E,et al.Characterizing the role of enterohepatic recycling in the interactions between mycophenolate mofetil and calcineurin inhibitors in renal transplant patients by pharmacokinetic modelling[J].Br J Clin Pharmacol,2005,60(3):249-256.
11. Sherwin C M T,Sagcal-Gironella A C P,Fukuda T,et al.Development of population PK model with enterohepatic circulation for mycophenolic acid in patients with childhood-onset systemic lupus erythematosus[J].Br J Clin Pharmacol,2011,73(5):727-740.
12. 焦正,沈杰,仲珑瑾,等.麦考酚酸肠肝循环药动学模型的建立[J].药学学报,2006,41(3): 272-276.
13. WANG XiaoXing,LIU WenFang,ZHENG Tian,et al. Population pharmacokinetics of mycophenolic acid and its glucuronide metabolite in lung transplant recipients with and without cystic fibrosis[J].Xenobiotica,2017,47(8):697-704.
14. Shum B,Duffull S B,Taylor P J,et al.Population pharmacokinetic analysis of mycophenolic acid in renal transplant recipients following oral administration of mycophenolate mofetil[J]. Br J Clin Pharmacol,2003,56(2):188-197.
15. LING Jing,SHI Jun,JIANG QiuDi,et al. Population pharmacokinetics of mycophenolic acid and its main glucuronide metabolite: a comparison between healthy Chinese and Caucasian subjects receiving mycophenolate mofetil[J].Eur J Clin Pharmacol,2015,71(6): 95-106.
16. Bullingham R E S,Nicholls A J,Kamm B R.Clinical pharmacokinetics of mycophenolate mofetil[J].Clin Pharmacokinet,1998,34(6):429-455.
17. 杨晶,鲁憬莉,张爱玲,等.与霉酚酸药动学、药效学相关基因多态性的研究进展[J].中国临床药学杂志,2016,25(5):324-328.