Human Biomonitoring for Environmental Chemicals (2006) / Chapter Skim
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Appendix C PBPK Modeling
Appendix C PBPK Modeling
Pages 278-286
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Appendix C PBPK Modeling By R.S.H.
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APPENDIX C 279 PD relationship and thus make a better prediction of the time course of drug effects resulting from a certain dose regimen for the compound of interests. Furthermore, PBPK models in combination with absorption simulation and quantitative structure-activity relationship (QSAR)
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280 HUMAN BIOMONITORING FOR ENVIRONMENTAL CHEMICALS AM1LU AM2LU Km, QP KF CI CX Vmax GAS QC QC LUNG QC CV CA1 CA EXCHANGE METABOLISM QR QR RICHLY PERFUSED CVR CA QF QF FAT CA CVF QS QS SLOWLY PERFUSED CA CVS QL QL LIVER CA CVL KZER KF Km, Vmax AM2L AM1L G.I. TRACT FIGURE C-1 A graphical representation of a physiologically based pharmacokinetic (PBPK)
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APPENDIX C 281 physical and chemical processes. In mammals, the physical processes (i.e., mass balance, thermodynamics, transport, and flow)
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282 HUMAN BIOMONITORING FOR ENVIRONMENTAL CHEMICALS where Vi represents the volume of tissue group i, Qi is the blood flow rate to tissue group i, CAj is the concentration of chemical j in arterial blood, and Cij and CVij are the concentrations of chemical j in tissue group i and in the effluent venous blood from tissue i, respectively. Metabij is the rate of metabolism for chemical j in tissue group i; liver, being the principal organ for metabolism would have significant metabolism and, with some exception, usually Metabij is equal to zero in other tissue groups.
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APPENDIX C 283 (or training set) to develop the model is necessary.
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284 HUMAN BIOMONITORING FOR ENVIRONMENTAL CHEMICALS process may be repeated again and again when necessary; such an iterative process is critically important for the development of a PBPK model. In that sense, PBPK modeling is a very good hypothesis-testing tool in toxicology and it may be utilized to conduct many different kinds of experiments on computer (i.e., in silico toxicology)
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APPENDIX C 285 enzyme kinetic information for many of the environmentally important chemicals are within easy reach for many laboratories. PBPK Models for Chemical Interactions (Interactive PBPK Models)
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286 HUMAN BIOMONITORING FOR ENVIRONMENTAL CHEMICALS Ramsey, J.C., and M.E. Andersen.
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