摘要
ThisstudydevelopedapopulationpharmacokineticmodelforsodiumtanshinoneIIAsulfonate(STS)inhealthyvolunteersandcoronaryheartdisease(CHD)patientsinordertoidentifysignificantcovariatesforthepharmacokineticsofSTS.Bloodsampleswereobtainedbyintensesamplingapproachfrom10healthyvolunteersandsparsesamplingfrom25CHDpatients,andapopulationpharmacokineticanalysiswasperformedbynonlinearmixed-effectmodeling.Thefinalmodelwasevaluatedbybootstrapandvisualpredictivecheck.Atotalof230plasmaconcentrationswereincluded,137fromhealthyvolunteersand93fromCHDpatients.Itwasatwo-compartmentmodelwithfirst-orderelimination.Thetypicalvalueoftheapparentclearance(CL)ofSTSinCHDpatientswithtotalbilirubin(TBIL)levelof10μmol(L?1was48.7L(h?1withinterindividualvariabilityof27.4%,whereasthatinhealthyvolunteerswiththesameTBILlevelwas63.1L(h?1.Residualvariabilitywasdescribedbyaproportionalerrormodelandestimatedat5.2%.TheCLofSTSinCHDpatientswaslowerthanthatinhealthyvolunteersanddecreasedwhenTBILlevelsincreased.Thebootstrapandvisualpredictivecheckconfirmedthestabilityandvalidityofthefinalmodel.TheseresultssuggestedthatSTSdosageadjustmentmightbeconsideredbasedonTBILlevelsinCHDpatients.
出版日期
2019年03月13日(中国期刊网平台首次上网日期,不代表论文的发表时间)