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

作者：Thompson Matthew D; Thompson Henry J^*

来源：Current Drug Targets, 2012, 13(14): 1876-1884.

• Biguanides
• cancer prevention
• pharmacokinetics
• pharmacodynamics
• metformin

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.

• 出版日期2012-12