药物非房室模型分析复习过程.ppt

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1、药物非房室模型分析ExamplesofStatisticalMomentUsageInstatisticsInphysicsM0NweightM1(mean)CenterofmassM2(variance)MomentofinertiaM3(skewness)M4(kurtosis)2Instatistics,themeanisameasureofasamplemeanandisactuallyanestimateofthetruepopulationmean.Inpharmacokinetics,wecancalculatethemome

2、ntofthetheoreticalprobabilitydensityfunction(i.e.,thesolutionofadifferentialequationdescribingtheplasmaconcentrationtimedata),orwecancalculatemomentsfrommeasuredplasmaconcentration-timedata.Thesecurvesarereferredtoassamplemomentsandareestimatesofthetruecurves.3Assumeatheor

3、eticalrelationshipofC(t)asafunctionoftime.Thenon-normalizedmoments,Sr,abouttheoriginarecalculatedas:4Non-normalizedmomentsKineticparameterAUCAreaunderthecurveAUMCAreaunderthemomentcurve5From:RowlandM,TozerTN.ClinicalPharmacokinetics–ConceptsandApplications,3rdedition,Willi

4、amsandWilkins,1995,p.487.6NormalizedmomentsKineticparameterFirstmoment:MRTMeanresidencetime7AREADETERMINATIONA.IntegrationofSpecificFunctionMustelucidatethespecificfunctionInfluencedbythequalityofthefit8B.NumericalIntegrationLineartrapezoidalLogtrapezoidal9B.NumericalInteg

5、rationLineartrapezoidal10B.NumericalIntegrationLineartrapezoidalAdvantages:Simple(cancalculatebyhand)Disadvantages:AssumesstraightlinebtwndatapointsIfcurveissteep,errormaybelargeUnderoroverestimatedependsonwhethercurveisascendingofdescending1112B.NumericalIntegrationLinear

6、trapezoidalLogtrapezoidal13B.NumericalIntegrationLineartrapezoidalLogtrapezoidalAdvantages:HandcalculatorVeryaccurateformono-exponentialVeryaccurateinlatetimepointswhereintervalbtwnpointsissubstantiallyincreasedDisadvantages:LimitedapplicationMayproducelargeerrorsonanascen

7、dingcurve,nearthepeak,orsteeplydecliningpolyexponentialcurve14B.NumericalIntegrationLineartrapezoidalLogtrapezoidalExtrapolationtoinfinityAssumeslog-lineardecline1516Time(hr)C(mg/L)02.5512.0031.1350.7070.43100.20180.025AUCDeterminationArea(mg-hr/L)-2.2753.131.831.130.9450.

8、900Total10.21AUMCDeterminationCxt(mg/L)(hr)02.003.393.503.012.000.45Area(mg-hr2/L)-1.005.