A Systems Pharmacokinetic and Pharmacodynamic Approach to Identify Opportunities and Pitfalls in Energy Stress-Mediated Chemoprevention: The Use of Metformin and Other Biguanides

Author(s): Matthew D. Thompson, Henry J. Thompson.

Journal Name: Current Drug Targets

Volume 13 , Issue 14 , 2012

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Abstract:

Metformin, a widely used anti-hyperglycemic drug in the biguanide class, is currently under investigation for the prevention of cancer. Surprisingly however, considering the time and cost of clinical chemoprevention trials and the current scrutiny of cancer chemoprevention, limited attention has been given to integrating available data, identifying the subpopulations most likely to benefit, or to quantitatively understanding the potential pitfalls of biguanide chemoprevention. Herein, a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic framework is proposed for integrating information on physicochemical, cell-based, animal, and human studies of various biguanides to identify gaps in knowledge and to build a systems model that may facilitate the planning of randomized cancer chemoprevention trials of metformin.

Keywords: Biguanides, cancer prevention, pharmacokinetics, pharmacodynamics, metformin

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Article Details

VOLUME: 13
ISSUE: 14
Year: 2012
Page: [1876 - 1884]
Pages: 9
DOI: 10.2174/138945012804545614
Price: $58

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