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Impact of Physiological Determinants: Flow, Binding, Transporters and Enzymes on Organ and Total Body Clearances

  • K. Sandy Pang
  • Huadong Sun
  • Edwin C.Y. Chow
Chapter

Abstract

Physiologically based pharmacokinetic (PBPK) models of the intestine, liver, and kidney were developed to examine the influence of transporters as well as enzymes on the area under the curve and clearances of drugs and metabolites. Whole body PBPK models were then developed, with the kidney and intestine or the kidney and liver as the organs for excretion and metabolism. From these PBPK models, the influence of flow, binding, transporters, and enzymes and the presence of competing pathways and competing organs on the areas of the drug and metabolite and total body clearance were defined. These relationships on the drug and metabolite AUC data are extremely useful for understanding the DDI mechanism, transport or metabolism, or both.

Keywords

PBPK Model Unbind Fraction Intrinsic Clearance Unbind Drug Unstirred Water Layer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The work is supported by the Canadian Institute for Health Research, CIHR (MOP89850).

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoCanada
  2. 2.NoAb BioDiscoveries Inc.MississaugaCanada

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