Pharmacologically based pharmacokinetic

Pharmacologically based pharmacokinetic (PBPK) models have also been incorporated into the assessment of responses to mixtures of some substances where interactions may occur. This was suggested for application in assessing human health risks of contaminants in drinking water (Krishnan et al. 1997) on the basis that most interactions between organic substances occur as a result of induction or inhibition of metabolism. This has been applied in predicting the maximal likely interaction in mixtures of chlorinated and nonchlorinated hydrocarbons (Haddad et al. 2000) and aromatic petroleum hydrocarbons (Haddad et al. 1999). Metabolic and other data are required for PBPK models, and, as these may only be available for a few organisms in the environment, they are not yet widely used for extrapolation. 

Elizabetli, C.M., Della, P., Oscar Ploeger, B.A. and Voskuyl, R.A. (2007) Mechanism-based pharmacokinetic-pharmacodynamic modeling hiophase distribution, receptor theory, and dynamical systems analysis. Annual Review of Pharmacology and Toxicology, 47, 357-400. 

FIGURE C-2 A flow chart illustrating processes involved in physiologically based pharmacokinetics. Source Andersen 1987. Reprinted with permission copyright 1987, Toxicology and Applied Pharmacology. 

In this chapter, the design strategy, synthesis, pharmacology, and pharmacokinetics of fluorinated conformationally restricted glutamate analogues are described in comparison with those of the corresponding hydrocarbon-based compounds. 

McDougal JN, Zheng Y, Zhang Q, Conolly R. Biologically based pharmacokinetic and pharmacodynamic models of skin. In Riviere JE, editor, Dermal absorption models in toxicology and pharmacology. New York Taylor and Francis, 2006. p. 89-112. 

Andersen, M., Clewell, H., Gargas, F., Smith, F., and Reitz, R. (1987). Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. Toxicology and Applied Pharmacology 87 185-202. 

Yokogawa, K., Ishizaki, J., Ohkuma, S., Miyamoto, K. (2002). Influence of hpophihcity and lysosomal accumulation on tissue distribution kinetics of basic drugs a physiologically based pharmacokinetic model. Methods and Finding in Experimental Clinical Pharmacology, 24, 81-93. 

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