title: A computational framework for interspecies pharmacokinetics, exposure and toxicity assessment of gold nanoparticles.
abstract: OBJECTIVE
  To develop a comprehensive computational framework to simulate tissue distribution of gold nanoparticles (AuNP) across several species.
  
  
  METHODS
  This framework was built on physiologically based pharmacokinetic modeling, calibrated and evaluated with multiple independent datasets.
  
  
  RESULTS
  Rats and pigs seem to be more appropriate models than mice in animal-to-human extrapolation of AuNP pharmacokinetics and that the dose and age should be considered. Incorporation of in vitro and/or in vivo cellular uptake and toxicity data into the model improved toxicity assessment of AuNP.
  
  
  CONCLUSIONS
  These results partially explain the current low translation rate of nanotechnology-based drug delivery systems from mice to humans. This simulation approach may be applied to other nanomaterials and provides guidance to design future translational studies.
authors.affiliation: Institute of Computational Comparative Medicine (ICCM), Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Zhoumeng
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Monteiro-Riviere
authors.affiliation: Department of Radiology, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Raghuraman
authors.initials: R
authors.lastname: Kannan
authors.affiliation: Institute of Computational Comparative Medicine (ICCM), Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D006046:Gold / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008954:Models, Biological; D053758:Nanoparticles / Q000633:toxicity*; D051381:Rats; D013045:Species Specificity; D013552:Swine; D014018:Tissue Distribution; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D006046:Gold
keywords: PBPK modeling; biodistribution; computational nanotoxicology; endocytosis; nanomaterials; phagocytosis; physiologically based pharmacokinetic modeling; toxicokinetics