Prediction of Human Pharmacokinetics

  • Siamak Cyrus Khojasteh
  • Harvey Wong
  • Cornelis E. C. A. Hop


The prediction of human pharmacokinetics is an extremely difficult endeavor during the selection of drug candidates for further human clinical testing. Despite a variety of available in vitro and in vivo methodologies, successful predictions are still difficult when performing them prospectively. This chapter gives a general overview of in vitro and in vivo methodologies used to predict human pharmacokinetics.


Hepatic Blood Flow PBPK Model Allometric Equation Microsomal Protein Intrinsic Clearance 
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List of Abbreviations


Absorption, distribution, metabolism, and excretion


Brain weight


Hepatic clearance


Intrinsic clearance


Unbound clearance




Fraction absorbed from the intestine


Fraction that escapes intestinal metabolism


Fraction that escapes hepatic metabolism


Unbound fraction in blood/plasma


Unbound fraction in microsomes


Unbound fraction in tissues


Hepatocytes per gram of liver


In vitro–in vivo extrapolation


Michaelis–Menten constant (i.e., substrate concentration when v is ½ of V max)


Maximum life span


Microsomal protein per gram of liver


Mean residence time


Cytochrome P450


Physiologically based pharmacokinetic model




Amount of microsomal protein in the incubation


Hepatic blood flow


Ratio of binding proteins in extracellular fluid (except plasma) to binding proteins in plasma

t1/2(in vitro)

In vitro half-life


Volume of distribution


Unbound volume of distribution


Extracellular fluid volume


Incubation volume


Maximum rate of the metabolic reaction


Plasma volume


“Remainder” of the fluid volume


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Siamak Cyrus Khojasteh
    • 1
  • Harvey Wong
    • 1
  • Cornelis E. C. A. Hop
    • 1
  1. 1.Genentech, Inc.San FranciscoUSA

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