Pharmacodynamic cancer model

Risk Assessment. This model successfully described the disposition of chloroform in rats, mice and humans following various exposure scenarios and developed dose surrogates more closely related to toxicity response. With regard to target tissue dosimetry, the Corley model predicts the relative order of susceptibility to chloroform toxicity consequent to binding to macromolecules (MMB) to be mouse > rat > human. Linking the pharmacokinetic parameters of this model to the pharmacodynamic cancer model of Reitz et al. (1990) provides a biologically based risk assessment model for chloroform. 

Chung YL et al. Magnetic resonance spectroscopic pharmacodynamic markers of the heat shock protein 90 inhibitor 17-allylamino,17-demethoxygeldanamycin (17AAG) in human colon cancer models. J Natl Cancer Inst 2003 95 1624-1633. 

Bonfils, C., Kalita, A., Dubay, M Siu, L.L, Carducd, M.A., Reid, G Martell, R.E., Besterman, J.M. and Li, Z. (2008) Evaluation of the pharmacodynamic effects of MGCD0103 from preclinical models to human using a novel HDAC enzyme assay. Clinical Cancer Research, 14, 3441-3449. 

N. M. S. Al-Saffar, H. Troy, A. Ramirez de Molina, L. E. Jackson, B. Madhu, J. R. Griffiths, M. O. Leach, P. Workman, J. C. Lacal, 1. R. Judson and Y.-L. Chung, Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of the choline kinase inhibitor MN58b in human carcinoma models. Cancer Res., 2006,66,427-434. 

Excerpted primarily from Yang, R.S.H., M.E. Andersen, J.E. Dennison, Y.C. Ou, K.H. Liao, and B. Reisfeld, 2004. Physiologically based pharmacokinetic and pharmacodynamic modeling. Pp. 391-405 in Mouse Models of Cancer. E.C. Holland, ed., Wiley New York. Reprinted with permission copyright 2004, Wiley. 

Minami H, Ratain MJ, Ando Y, Shimokata K. Pharmacodynamic modeling of prolonged administration of etoposide. Cancer Chemother Pharmacol 1996 39(l-2) 61-6. 

Dose-response models describe a cause-effect relationship. There are a wide range of mathematical models that have been used for this purpose. The complexity of a dose-response model can range from a simple one-parameter equation to complex multicompartment pharmacokinetic/pharmacodynamic models. Many dose-response models, including most cancer risk assessment models, are population models that predict the frequency of a disease in a population. Such dose-response models typically employ one or more frequency distributions as part of the equation. Dose-response may also operate at an individual level and predict the severity of a health outcome as a function of dose. Particularly complex dose-response models may model both severity of outcome and population variability, and perhaps even recognize the influence of multiple causal factors. 

Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cancer Res 64 1094-1101 (2004). 

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