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Perhaps this is two birds with one stone!
As Prasa mentioned in vitro - in vivo extrapolation (IVIVE) mainly
means the use of in vitro as well as physiological, genetic and even
epidemiological data to predict the fate of drugs in the human body,
the following paper in Nature gives a quick background on this:
Rostami-Hodjegan A and Tucker GT (2007) Simulation and prediction of
in vivo drug metabolism in human populations from in vitro data. Nat
Rev Drug Discov 6:140-148.
(freely available at: http://delivery.fostereprints.com/?
In an interesting application, the IVIVE approach was combined with
clinical trial simulation to assess different elements of the study
design which could be used a priori to avoid inconclusive
pharmacogenetic studies; the authors considered the effect of CYP2D6
polymorphism on pharmacokinetics and pharmacodynamics.
Dickinson GL, Rezaee S, Proctor NJ, Lennard MS, Tucker GT and Rostami-
Hodjegan A (2007) Incorporating in vitro information on drug
metabolism into clinical trial simulations to assess the effect of
CYP2D6 polymorphism on pharmacokinetics and pharmacodynamics:
dextromethorphan as a model application. J Clin Pharmacol 47:175-186.
In another similar study the impact of genetic polymorphisms of
CYP2C9 was also considered.
Dickinson GL, Lennard MS, Tucker GT and Rostami-Hodjegan A (2007) The
use of mechanistic DM-PK-PD modelling to assess the power of
pharmacogenetic studies -CYP2C9 and warfarin as an example. Br J Clin
In both of these papers the Simcyp algorithms were used. The Simcyp
simulator includes numerous databases containing human physiological,
genetic and epidemiological information for different populations. By
integrating this information with the drug dependent in vitro data
the simulator allows you to simultaneously predict the PK behaviour
of the parent compound and its metabolite as well as their metabolic
interactions using physiologically-based PK (PBPK) models.
Hope this helps.
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