白藜芦醇苷及其代谢物在Beagle犬体内的排泄动力学研究
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摘要
目的:研究白藜芦醇苷(TRG)及其代谢物在Beagle犬粪样中的代谢与排泄情况,为TRG的新药开发提供实验依据。方法:4只Beagle犬ig TRG 20%聚乙二醇400溶液50 mg/kg,采用液相色谱-质谱联用法鉴定TRG给药后12~24 h粪样中的代谢物,采用高效液相色谱法测定给药后0~12、12~24、24~36、36~48、48~72、72~96 h TRG在粪样中主要代谢物[其苷元白藜芦醇(TR)]以及TR累积排泄率及排泄速率。结果:在犬粪中可测到TR及TR的2个硫酸结合物,其中TR为主要代谢物,未测到TRG。TR在犬粪中排泄速率于给药后12~24 h时最大,达到9.65 mg/h;其累积排泄率为39.3%,相当于TRG给药剂量的67.2%。结论:犬ig TRG后,TRG主要以TR形式从粪中排出体外。
OBJECTIVE:To study the metabolite and excretion of polydatin(Trans-resveratrol-3-O-glucoside,TRG) and its metabolites in Beagle dog feces,and provide experimental basis for the new drug development of TRG. METHODS:4 Beagle dogs were intragastrically administrated TRG 20% polyethylene glycol 400 solution 50 mg/kg. LC/MS was used to identify the metabolites of TRG in dog feces after 12-24 h of administration,and HPLC was adopted to determine the cumulative excretion rate and excretion speed rate of the major metabolite resveratrol(TR)in feces samples after 0-12,12-24,24-36,36-48,48-72,72-96 h of administration. RESULTS:TR and two sulfate conjugates of TR were found in dog feces,and TR was a major metabolite,while TRG was undetermined. The excretion speed rate of TR in dog feces was the rapidest after 12-24 h of administration,reaching 9.65 mg/h. Its cumulative excretion rate was 39.3%,equivalent to 67.2% of TRG. CONCLUSIONS:After TRG is intragastrically administrated to dogs,TRG was mainly excreted in the form of TR via dog feces.
OBJECTIVE:To study the metabolite and excretion of polydatin(Trans-resveratrol-3-O-glucoside,TRG) and its metabolites in Beagle dog feces,and provide experimental basis for the new drug development of TRG. METHODS:4 Beagle dogs were intragastrically administrated TRG 20% polyethylene glycol 400 solution 50 mg/kg. LC/MS was used to identify the metabolites of TRG in dog feces after 12-24 h of administration,and HPLC was adopted to determine the cumulative excretion rate and excretion speed rate of the major metabolite resveratrol(TR)in feces samples after 0-12,12-24,24-36,36-48,48-72,72-96 h of administration. RESULTS:TR and two sulfate conjugates of TR were found in dog feces,and TR was a major metabolite,while TRG was undetermined. The excretion speed rate of TR in dog feces was the rapidest after 12-24 h of administration,reaching 9.65 mg/h. Its cumulative excretion rate was 39.3%,equivalent to 67.2% of TRG. CONCLUSIONS:After TRG is intragastrically administrated to dogs,TRG was mainly excreted in the form of TR via dog feces.
引文
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[16]蔡茁,俞发,马安德,等.白藜芦醇苷在Beagle犬体内的药代动力学研究[J].南方医科大学学报,2009,29(8):1538-1540.
[2]Wang HL,Gao JP,Han YL,et al.Comparative studies of polydatin and resveratrol on mutual transformation and antioxidative effect in vivo[J].Phytomedicine,2015,22(5):553-559.
[3]Du QH,Peng C,Zhang H.Polydatin:a review of pharmacology and pharmacokinetics[J].Pharm Biol,2013,51(11):1347-1354.
[4]徐冰,林焕冰,王茜,等.白藜芦醇苷对脑缺血再灌注模型大鼠的保护作用[J].中国药房,2013,24(13):4040-4042.
[5]张明,鞠楷,孙琴,等.西南5个产区虎杖中虎杖苷和白藜芦醇含量比较[J].中国药房,2012,23(39):3723-3725.
[6]郭茜,孟宪生,包永睿,等.HPLC双波长等基线融合结合校正因子法测定虎杖中3种成分的含量[J].中国药房,2013,24(47):4461-4464.
[7]Zhang ZC,Xu M,Sun SF,et al.Metabolic analysis of four phenolic acids in rat by liquid chromatography-tandem mass spectrometry[J].J Chromatogr B,2008,871(1):7-14.
[8]Wang D,Zhang Z,Ju J,et al.Investigation of piceid metabolites in rat by liquid chromatography tandem mass spectrometry[J].J Chromatogr B,2011,879(1):69-74.
[9]Ding XY,Hou XL,Gao SH,et al.Pharmacokinetics and bioavailability study of polydatin in rat plasma by using a LC-MS/MS method[J].Pak J Pharm Sci,2014,27(6):1931-1937.
[10]He H,Zhao Y,Chen X,et al.Quantitative determination of trans-polydatin,a natural strong anti-oxidative compound,in rat plasma and cellular environment of a human colon adenocarcinoma cell line for pharmacokinetic studies[J].J Chromatogr B,2007,855(2):145-151.
[11]Lv CY,Zhang LT,Wang Q,et al.Determination of piceid in rat plasma and tissues by high-performance liquid chromatographic method with UV detection[J].Biomed Chromatogr,2006,20(11):1260-1266.
[12]Gao SH,Fan GR,Hong ZY,et al.HPLC determination of polydatin in rat biological matrices:application to pharmacokinetic studies[J].J Pharm Biomed Anal,2006,41(1):240-245.
[13]Zhou SY,Yang RT,Teng ZH,et al.Dose-dependent absorption and metabolism of trans-polydatin in rats[J].J Agric Food Chem,2009,57(11):4572-4579.
[14]Zhang WT,Li Q,Zhu M,et al.Direct determination of polydatin and its metabolite in rat excrement samples by high-performance liquid chromatography[J].Chem Pharm Bull,2008,56(11):1592-1595.
[15]林建海,李笑宏,唐跃年,等.白藜芦醇苷的HPLC法分析及其在苗猪体内的药代动力学研究[J].药物分析杂志,2001,21(5):325-328.
[16]蔡茁,俞发,马安德,等.白藜芦醇苷在Beagle犬体内的药代动力学研究[J].南方医科大学学报,2009,29(8):1538-1540.