Physiologically based models model parameters

Simulation methods have also been developed that include physiologically based pharmacokinetic modeling (PBPK) and methods such as Cloe PK, OMPPPlus, GastroPlus , SimCYP , and others [122] that are described elsewhere in this book. It is likely that the computational metabolism predictions could be integrated with these to assist in deriving more accurate predictions of human pharmacokinetic parameters. 

Cronin WJ, Oswald EJ, Shelley ML, et al. 1995. A trichloroethylene risk assessment using a Monte Carlo analysis of parameter uncertainty in conjunction with physiologically-based pharmacokinetic modeling. Risk Anal 15 555-565. 

Physiologically based pharmacokinetic models provide a format to analyze relationships between model parameters and physicochemical properties for a series of drug analogues. Quantitative structure-pharmacokinetic relationships based on PB-PK model parameters have been pursued [12,13] and may ultimately prove useful in the drug development process. In this venue, such relationships, through predictions of tissue distribution, could expedite drug design and discovery. 

RP Brown, MD Delp, SL Lindstedt, LR Rhomberg, RP Beliles. Physiological parameter values for physiologically based pharmacokinetic models. Toxicol Ind Health 13 407-484, 1997. 

Absorbed lead is distributed in various tissue compartments. Several models of lead pharmacokinetics have been proposed to characterize such parameters as intercompartmental lead exchange rates, retention of lead in various pools, and relative rates of distribution among the tissue groups. See Section 2.3.5 for a discussion of the classical compartmental models and physiologically based pharmacokinetic models (PBPK) developed for lead risk assessments. 

Clewell HJ, Lee T, Carpenter RL. 1994. Sensitivity of physiologically based pharmacokinetic models to variation in model parameters methylene chloride. Risk Analysis 14 521-531. 

H. K., Uncertainties in physiologically based pharmacokinetic models caused by several input parameters, bit. Arch. Occup. Environ. Health 1999, 72, 247— 254. 

A physiologically based pharmacokinetic model for predicting ethylene dibromide kinetics and consequent toxicity, based on in-vitro metabolic parameters of rodents and humans and on the use of scaling factors, has been presented (Ploemen et al., 1997). Its most important prediction is that the GST pathway is significantly active even at low ethylene dibromide concentrations, which has important implications for risk assessment. 

Thomann (1989) and Gobas (1993) have developed physiologically based kinetic models, including rate constants for chemical uptake and elimination based on physiological parameters such as gill ventilation rates, feeding rates and chemical assimilation rates as well as empirical correlations. Tables 9.6 and 9.7 list the model equations and parameters. 

CLEWELL, H.J., LEE, T.S. and CARPENTER, R.L. (1994). Sensitivity of physiologically-based pharmacokinetics models to variation in model parameters Methylene chloride, Risk Anal. 14, 533-554. 

Hattis D, Ginsberg G, Sonawane B, Smolenski S, Russ A, Kozlak M, Goble R (2003) Differences in pharmacokinetics between children and adults — II. Children s variability in drug elimination half-lives and in some parameters needed for physiologically-based pharmacokinetic modeling. Risk Anal, 23 117-142. 

Various physiologically based pharmacokinetic models for chloroform have been described using physiological and metabolic parameter values for rats, dogs, and humans to exercise the models. 

Roy A, Weisel CP, Lioy PJ, Georgopoulos PG. A distributed parameter physiologically-based pharmacokinetic model for dermal and inhalation exposure to volatile organic compounds. Risk Anal 1996 16 147-60. 

Building a Physiologically Based Biokinetic Model on the Basis of In Vitro-Determined Parameters... 

Bosgra S, van Eijkeren J, Bos P, Zeilmaker M, Slob W (2012) An improved model to predict physiologically based model parameters and their inter-individual variability from anthropometry. Crit Rev Toxicol 42 751-767. doi 10.3109/10408444.2012.709225... 

Physiologic model-physiologically based pharmacokinetic model (PB/PK) A physiologically based model for Gl transit and absorption in humans is presented. The model can be used to study the dependency of the fraction dose absorbed (Fabs) of both neutral and ionizable compounds on the two main physico-chemical input parameters [the intestinal permeability coefficient (Pint) and the solubility in the intestinal fluids (Sint)] as well as the physiological parameters, such as the gastric emptying time and the intestinal transit time. For permeability-limited compounds, the model produces the established sigmoidal dependence between Fabs and Pnt. In case of solubility-limited absorption, the model enables calculation of the critical mass-solubility ratio, which defines the onset of nonlinearity in the response of fraction absorbed to dose. In addition, an analytical equation to calculate the intestinal permeability coefficient based on the compound s membrane affinity and MW was used successfully in combination with the PB-PK model to predict the human fraction dose absorbed of compounds with permeability-limited absorption. Cross-validation demonstrated a root-mean-square prediction error of 7% for passively absorbed compounds. 

Parameters Used in the Physiologically Based Pharmacokinetic Model for 2-Butoxyethanol and 2-Butoxyacetic Acid... 

De Jong, L.P.A., Determination of parameters for development of a physiologically based model for the toxicokinetics of C( )P( )-soman. Final Report for Cooperative Agreement DAMD17-92-V-2004, 1993. 

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