达立通浸膏中延胡索乙素、川陈皮素和木香烃内酯在大鼠体内的药代动力学及组织分布研究OA北大核心CSTPCD
Pharmacokinetics and tissue distribution of tetrahydropalmatine,nobiletin,and costunolide in rats after oral administration of Dalitong extract
目的:研究达立通浸膏给药后大鼠体内主要药物成分及药代动力学特点.方法:建立同时检测延胡索乙素、川陈皮素和木香烃内酯的超高效液相色谱-串联质谱(UPLC-MS/MS)方法,应用于测定大鼠血浆和组织中药物浓度及药代动力学特征.结果:建立了同时定量测定延胡索乙素、川陈皮素和木香烃内酯方法,单次灌胃给予达立通浸膏后,延胡索乙素、川陈皮素和木香烃内酯可以快速吸收进入体内,在血中峰浓度(Cmax)分别为(13.73±7.50)、(27.01±17.69)、(66.73±29.94)ng/mL,曲线下 面积(AUCo-t)分别为(80.43±40.03)、(41.30±28.69)、(303.90±136.69)ng·h·mL-1,消除半衰期(t1/2)分别为(5.82±2.22)、(1.08±0.01)、(4.95±2.53)h.多次给药能明显增加各物质体内暴露水平.各成分在大鼠的主要组织/器官中广泛分布,在胃肠道中暴露水平最高,其次是肝和肾.各成分存在明显的雌雄差异,在雌性大鼠中的暴露量(Cmax和AUC)均显著高于雄性大鼠(P＜0.05).结论:UPLC-MS/MS测定延胡索乙素、川陈皮素和木香烃内酯的方法准确、灵敏、可靠.达立通浸膏中延胡索乙素、川陈皮素和木香烃内酯可吸收进入血液、广泛分布于体内组织、器官、较快代谢/消除,为达立通浸膏潜在的体内药代标记物.
AIM:To investigate the pharmacoki-netic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS/MS.METHODS:An UPLC-MS/MS method was established to simultaneously detect tetrahydropalmatine,nobiletin and costunolide in the plasma and tissues of SD rats.The method was applied to investigate the pharmacokinetic charac-teristics and tissue distribution.RESULTS:After a single oral administration,the three active compo-nents were rapidly absorbed into the body,with a peak concentration(Cmax)of(13.73±7.50),(27.01± 17.69)and(6.73±29.94)ng/mL for tetrahydropal-matine,nobiletin,and costunolide,respectively.The time to reach the peak concentration(Tmax)was(1.40±0.93),(0.63±0.28)and(2.38±8.81)h,re-spectively.The area under the curve(AUC)was(80.43±40.03),(41.30±28.69)and(303.90±136.69)ng·h·mL-1,respectively,and the elimination half-life(t1/2)was(5.82±2.22),(1.08±0.01)and(4.95± 2.53)h,respectively.Multiple dosing significantly in-creased the exposure of the three components.There were significant differences in exposure be-tween male and female rats,with higher exposure observed in female rats(P＜0.05).The three active components were widely distributed in various tis-sues/organs,with the highest exposure observed in the gastrointestinal tract,followed by the liver and kidney.CONCLUSION:The UPLC-MS/MS method is accurate,sensitive,and reliable for the quantitative analysis of tetrahydropalmatine,nobiletin,and cos-tunolide.These three active components in Dali-tong extract can be absorbed,widely distributed in various tissues or organs,and rapidly metabolized/eliminated after oral administration.They are po-tential pharmacokinetic markers of Dalitong extract.
张渊茂;张冉;廖睿伟;陶琳;孟秀秀;徐晨;高芳芳;阿基业;王广基
中国药科大学药物代谢动力学重点实验室,南京 210009,江苏南昌弘益药业有限公司,南昌 330006,江西
药学
达立通浸膏延胡索乙素川陈皮素木香烃内酯药物代谢动力学组织分布
Dalitong extracttetrahydropalma-tinenobiletincostunolidepharmacokineticstis-sue distribution
《中国临床药理学与治疗学》 2024 (001)
37-51 / 15
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