摘要
目的 阐明中药复方药物动力学与谱动学总量统计矩的数学模型与参数关系,示范性地用补阳还五汤中 11 种成分进行药物动力学与谱动学研究,探讨其量-时关系,包括代谢时间和色谱保留时间关系.方法 采用HPLC/MS法测定补阳还五汤中黄芪甲苷等 11 种成分的药物浓度,并根据已建立的中药药物动力学与谱动学的总量统计矩数学模型,计算药物动力学与谱动学参数.结果 补阳还五汤中11种成分的药物动力学总量统计矩参数分别为AUCT为432.9 ng·h·mL-1,MRTT为2.185 h,VRTT为5.259 h2;CLT为 82.95 mL·h-1;VT为 139.9 mL;95%的代谢时间区间为[0,6.680]h.谱动学的 VUCT为 457.5 ng·h·min·mL-1;MCRTT为5.625 min;VCRTT为 7.949 min2,95%的时间区间为[0.098 98,11.15]min.各取样点的谱动学总量零、一、二阶矩的RSD分别为86.09%、2.299%、7.587%,相似度基本上都在 0.875以上.结论 中药药物动力学与谱动学总量统计矩法能表征多成分代谢的量-时关系,其中谱动学还能表征所测定代谢成分的构成比的变化和色谱学特征,可为临床合理用药奠定理论与实验研究基础.
Abstract
Objective To elucidate the mathematical model and parameter relationship of the total statistical moment between polypharmacokinetics and chromatopharmacokinetics of the Chinese medicine compound formulas,to demonstrate the polypharmacokinetics and chromatopharmacokinetics study of 11 components in Buyang Huanwu Decoction(BYHWD),and to explore their dose-time relationship,including the metabolic time and chromatographic retention time.Methods HPLC/MS was used to determine the concentrations of 11 components such as astragaloside IV in BYHWD,and the polypharmacokinetic and chromatopharmacokinetic parameters were calculated based on the established total statistical moment mathematical model of Chinese medicine.Results The total moment parameters of polypharmacokinetics of AUCT,MRTT,VRTT,CLT,and VT of the 11 components in BYHWD were 432.9 ng·h·mL-1,2.185 h,5.259 h2,82.59 mL·h-1,and 139.9 mL respectively,and the 95%metabolic time interval was from 0 to 6.680 h.The total moment parameters of chromatopharmacokinetics of VUCT,MCRTT,and VCRTT were 457.5 ng·h·min·mL-1,5.625 min,and 7.949 min2 respectively,with a 95%time interval from 0.098 98 to 11.15 min.The RSD of the total zero,first,and second moments of chromatopharmacokinetics at each sampling time-point were 86.09%,2.299%,and 7.587%respectively,with the similarity basically above 0.875.Conclusion The total statistical moment method of polypharmacokinetics and chromatopharmacokinetics of Chinese medicine can represent the dose-time relationship of multi-component metabolism.Among them,the chromatopharmacokinetics can also represent the compositional changes and chromatographic characteristics of the measured metabolic components,laying a theoretical and experimental research foundation for clinical rational medication.
基金项目
国家自然科学基金(82274215)
国家自然科学基金(81874507)
湖南省重点研发计划(2022SK2014)
湖南省自然科学基金(2022JJ30453)
湖南省科药联合基金(2021JJ80058)
全国名老中医药专家陈新宇传承工作室建设项目(国中医药人教函[2022]75号)
维普
万方数据