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@PHDTHESIS{Thiel:706432,
      author       = {Thiel, Christoph Werner Josef},
      othercontributors = {Blank, Lars Mathias and Sáez Rodríguez, Julio},
      title        = {{M}ultiscale modeling of drug-induced toxicity in humans},
      school       = {RWTH Aachen University},
      type         = {Dissertation},
      address      = {Aachen},
      reportid     = {RWTH-2017-08645},
      pages        = {1 Online-Ressource (209 Seiten) : Illustrationen,
                      Diagramme},
      year         = {2017},
      note         = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
                      University; Dissertation, RWTH Aachen University, 2017},
      abstract     = {Drug toxicity poses a crucial problem in drug development
                      and particularly in clinical care and in publichealth.
                      Although in vitro experiments can obtain valuable
                      information of the mechanisms underlyingdrug-induced
                      toxicity, there is still a clear lack of approaches
                      translating such in vitro findings into apatient situation.
                      In this thesis, a novel translational approach is presented
                      and is successfully applied inthree different studies to
                      investigate the onset of adverse drug events at patient
                      level. Here, multiscalemodeling enables the coupling of in
                      vitro concentration-response relationships, at the cellular
                      level, withdrug concentration-time profiles, at the organism
                      level, to predict cellular responses following drug
                      administrationof different doses in vivo. The application of
                      the developed translational approach allowedstudying
                      drug-induced toxicity in humans (i) for acute and chronic
                      administration of azathioprine in aproof-of-concept study,
                      (ii) for fifteen hepatotoxic drugs in a comparative manner
                      focusing on drug administrationof therapeutic and toxic
                      doses, and (iii) for a drug combination therapy of
                      acetaminophenand caffeine. The presented translational
                      approach may lead to useful knowledge for clinical
                      applicationgained from in vitro experiments thereby
                      contributing to the ongoing discussion of the predictive
                      valueof preclinical research. Overall, the results shown
                      here provide novel insights into drug-induced toxicitywithin
                      a patient context and, thus, may improve patient safety in
                      drug development.},
      cin          = {160000 / 161710},
      ddc          = {570},
      cid          = {$I:(DE-82)160000_20140620$ / $I:(DE-82)161710_20140620$},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2017-08645},
      url          = {https://publications.rwth-aachen.de/record/706432},
}