Prediction of the Pharmacokinetic Parameters of Triptolide in Rats Based on Endogenous Molecules in Pre-Dose Baseline Serum 英文参考文献.docVIP

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Prediction of the Pharmacokinetic Parameters of Triptolide in Rats Based on Endogenous Molecules in Pre-Dose Baseline Serum 英文参考文献.doc

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Prediction of the Pharmacokinetic Parameters of Triptolide in Rats Based on Endogenous Molecules in Pre-Dose Baseline Serum 英文参考文献

PredictionofthePharmacokineticParametersof TriptolideinRatsBasedonEndogenousMoleculesin Pre-DoseBaselineSerum LinshengLiu1.,BeiCao1.,JiyeAa1*,TianZheng1,JianShi1,MengjieLi1,XinwenWang1,ChunyanZhao1, WenjingXiao1,XiaoyiYu1,RunbinSun1,RongrongGu1,JunZhou1,LiangWu1,GangHao1, XuanxuanZhu2,GuangjiWang1* 1Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China, 2Jiangsu ProvincialHospitalofTraditionalChineseMedicine,Nanjing,Jiangsu,China Abstract Background:Individualvariancesusuallyaffectdrugmetabolismanddisposition,andhenceresultineitherineffectiveness ortoxicityofadrug.Inadditiontogeneticpolymorphism,themultipleconfoundingfactorsoflifestyles,suchasdietary preferences, contribute partially to individual variances. However, the difficulty of quantifying individual diversity greatly challengestherealizationofindividualizeddrugtherapy.Thisstudyaimsatquantitativeevaluatingtheassociationbetween individualvariancesandthepharmacokinetics. Methodology/Principal Findings: Molecules in pre-dose baseline serum were profiled using gas chromatography mass spectrometrytorepresenttheindividualvariancesofthemodelratsprovidedwithhighfatdiets(HFD),routinechowsand calorie restricted (CR) chows. Triptolide and its metabolites were determined using high performance liquid chromatography mass spectrometry. Metabonomic and pharmacokinetic data revealed that rats treated with the varied dietshaddistinctlydifferentmetabolicpatternsandshoweddifferentialCmax values,AUCanddrugmetabolismafteroral administration of triptolide. Rats with fatty chows had the lowest Cmax and AUC values and the highest percentage of triptolide metabolic transformation, while rats with CR chows had the highest Cmax and AUC values and the least percentageoftriptolidetransformation.Multivariatelinearregressionrevealedthatinbaselineserum,theconcentrationsof creatinineandglutamicacid,whichistheprecursorofGSH,werelinearlynegati