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UseEofEpharmacokinetic,EpharmacodynamicEandEpharmacogeneticEsoftwareE
forEmodelingEandETDM.ESpecialEsoftwareECMwPharm++/Edsim++REenableEtoE
demonstrateEtheEbehaviourEofEdrugsEinEhumanEorganism.
DoušadJ/E
AdPotůčekdJ/+
AdPuntdN/(
EdInstitutedofdPharmacologyAdFirstdFacultydofdMedicinedanddGeneraldTeachingdHospitalAd
CharlesdUniversitydindPragueAdCzechdrepublic
+dDepartmentdofdPharmacologyAdThirddFacultydofdMedicinedCharlesdUniversityAdPragueAd
CzechdRepublic
(dDepartmentdofdPharmacologydanddToxicologyAdUniversitydofdMaastrichtAdMaastrichtAd
Netherlands
BackgrounddApplyingdPKqPDdmodelsdindadclinicald
settingd provedd tod bed ad difficultd taskd ind thed pastd
becaused ofd thed complexityd ofd thed requiredd PKqPDd
modelingd software/d Recentlyd wered upgradedd twod
existingd pharmacokineticd softwared applications/d
Edsimxxd isd usedd ford developingd andd visuallyd
designingd PKqPDd modelsAd whiled MwPharmxxd isd
aimedd atd routined clinicald practiced ford dosed
calculationsdanddtherapeuticddrugdmonitoring/
ObjectiveE Thed aimd ofd thed studyd wasd tod processd
tolbutamided cased studyd withd thed softwared andd
demostrated thed optiond tod used thed softwared ford
modelingdcasedstudies/
Methodsd Insulind compartmentsd representedd byd thed
insulind minimald modeld andd glucosed compartmentsd
representedd byd thed glucosed minimald modeld wered
preparedd zFig/d Eb/d Thesed compartmentsd ared alwaysd
associateddwithdeachdother/dInsulinedhasdtwodeffectsd–d
itdstimulatesdcellulardglucosedupdatedandditdstimulatesd
glycogendsynthesys/dTolbutamidedindthisdmodeldhasd
effectsd –d itd stimulatesd thed insulind responsed andd
increasesdglucosedsensitivitydofdthedβKcells/
ConclusionsdThedvisualdmodelingdapproachdofdEdsimxxdgreatlydsimplifiesdtheddevelopmentdofdcomplexdmodelsd
whichd ared easilyd transferrabled tod MwPharmxx/d Thesed modelsd cand bed employedd ind ad clinicald environmentd
providingdtheddosagedregimendanddoptimalizationdbaseddondlargeddatabasedofdpharmacokineticqpharmacodynamicq
pharmacogeneticd drugd parametersd andd individuald patientd physiologicald parameters/d Thed previousd versiond ofd
MwPharmdapplicationdobtaineddthedhighestdscoredindthedTBenchmarkingdTherapeuticdDrugdMonitoringdSoftware:d
AdReviewdofdAvailabledComputerdToolsTdcarrieddoutdbydFuchsdetdal/dzClindPharmacokinetd+wE(0d–+zEb:SK++b/
Resultsd Performingd thed simulationsAd thed insulined
responsed basedd ond tolbutamided leveld ford thed
individualdpatientdwasdobtaineddzFig/d+b/
Fig. 1: PK/PD model of the tolbutamide study.
Fig. 2: Simulation curves of the PK/PD model.

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