Application of PBPK modelling in drug discovery and development at Pfizer.

Xenobiotica 2012 Jan 30;42(1):94-106. Epub 2011 Oct 30.

Pfizer Worldwide R&D, Department of Pharmacokinetics, Dynamics and Metabolism, Sandwich, Kent, UK.

Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to 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 realize its application and utility more broadly.

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http://dx.doi.org/10.3109/00498254.2011.627477DOI Listing
January 2012
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References

(Supplied by CrossRef)

Almond LM et al.
Curr Drug Metab 2009

Baxter LT et al.
Cancer Res 1994

Björkman S et al.
J Pharm Sci 2001

Brightman FA et al.
Drug Metab Dispos 2005

Brightman FA et al.
Drug Metab Dispos 2005

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