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10.1208/s12248-012-9446-2

http://scihub22266oqcxt.onion/10.1208/s12248-012-9446-2
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23269526DoseSelectionBasedonPhysiologicallyBasedPharmacokinetic(PBPK)Approaches.!3675752!23269526
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suck abstract from ncbi


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pmid23269526      AAPS+J 2013 ; 15 (2): 377-87
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  • Dose selection based on physiologically based pharmacokinetic (PBPK) approaches #MMPMID23269526
  • Jones HM; Mayawala K; Poulin P
  • AAPS J 2013[Apr]; 15 (2): 377-87 PMID23269526show ga
  • Physiologically based pharmacokinetic (PBPK) models are built using differential equations to describe the physiology/anatomy of different biological systems. Readily available in vitro and in vivo preclinical data can be incorporated into these models to not only estimate pharmacokinetic (PK) parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. They provide a mechanistic framework to understand and extrapolate PK and dose across in vitro and in vivo systems and across different species, populations and disease states. Using small molecule and large molecule examples from the literature and our own company, we have shown how PBPK techniques can be utilised for human PK and dose prediction. Such approaches have the potential to increase efficiency, reduce the need for animal studies, replace clinical trials and increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however some limitations need to be addressed to realise its application and utility more broadly.
  • |*Drug Dosage Calculations[MESH]
  • |*Models, Biological[MESH]
  • |*Pharmacokinetics[MESH]
  • |Animals[MESH]
  • |Biotransformation[MESH]
  • |Drug Administration Routes[MESH]
  • |Drug Discovery/*methods[MESH]
  • |Humans[MESH]
  • |Intestinal Absorption[MESH]
  • |Metabolic Clearance Rate[MESH]
  • |Pharmaceutical Preparations/*administration & dosage/*metabolism[MESH]
  • |Reproducibility of Results[MESH]
  • |Species Specificity[MESH]


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