A Bayesian population PBPK model for multiroute chloroform exposure

@article{Yang2010ABP,
  title={A Bayesian population PBPK model for multiroute chloroform exposure},
  author={Yuching Yang and Xu Xu and Panos G. Georgopoulos},
  journal={Journal of Exposure Science and Environmental Epidemiology},
  year={2010},
  volume={20},
  pages={326-341}
}
A Bayesian hierarchical model was developed to estimate the parameters in a physiologically based pharmacokinetic (PBPK) model for chloroform using prior information and biomarker data from different exposure pathways. In particular, the model provides a quantitative description of the changes in physiological parameters associated with hot-water bath and showering scenarios. Through Bayesian inference, uncertainties in the PBPK parameters were reduced from the prior distributions. Prediction… 

Figures and Tables from this paper

Bayesian Refinement of the Permeability-Limited Physiologically Based Pharmacokinetic Model for Perfluorooctanoic Acid in Male Rats.
TLDR
A hierarchical Bayesian analysis with Markov chain Monte Carlo was applied to reduce the uncertainty of parameters and improve the performance of the PBPK model, and the Bayesian framework could provide insights into the molecular mechanisms driving PFOA toxicokinetics.
Using Bayesian-PBPK modeling for assessment of inter-individual variability and subgroup stratification
TLDR
The presented Bayesian-PBPK approach systematically characterizes inter-individual variability within a population by updating prior knowledge about physiological parameters with new experimental data and allows, in combination with Bayesian approaches, the iterative assessment of specific populations by integrating information from several drugs.
Evaluation and calibration of high-throughput predictions of chemical distribution to tissues
TLDR
Through careful evaluation of predictive methods for chemical partitioning into tissues, improved and calibrated these methods and quantified confidence for TK predictions in humans and rats are improved and calibration of the model improved performance.
Simultaneous Ivabradine Parent-Metabolite PBPK/PD Modelling Using a Bayesian Estimation Method.
TLDR
A joint parent-metabolite physiologically based pharmacokinetic/pharmacodynamic model to predict the PK and PD of ivabradine and its metabolite following intravenous or oral administration is developed and can be scaled to other populations or used for investigation of untested scenarios.
Key Factors for Improving the Carcinogenic Risk Assessment of PAH Inhalation Exposure by Monte Carlo Simulation
TLDR
Data from a large-scale investigation of individual polycyclic aromatic hydrocarbon exposure was used to explore the key factors for improving the Monte Carlo simulation method and suggested that accurate simulation of exposure concentration and adjustment of correlated parameters could greatly improve the MCS.
...
1
2
3
4
...

References

SHOWING 1-10 OF 68 REFERENCES
Bayesian population analysis of a harmonized physiologically based pharmacokinetic model of trichloroethylene and its metabolites.
Statistical analysis of Fisher et al. PBPK model of trichloroethylene kinetics.
  • F. Bois
  • Biology
    Environmental health perspectives
  • 2000
TLDR
Two physiologically based pharmacokinetic models for trichloroethylene (TCE) in mice and humans were calibrated with new toxicokinetic data sets, and differences between human males and females in the toxicokinetics of TCE are pointed to.
Revised assessment of cancer risk to dichloromethane: part I Bayesian PBPK and dose-response modeling in mice.
Statistical issues in toxicokinetic modeling: a bayesian perspective.
TLDR
This work has developed an approach to toxicokinetic modeling that can be applied to heterogeneous human or animal populations and expands the possibilities for uncertainty analysis.
Population toxicokinetics of benzene.
TLDR
The distribution and metabolism of benzene in humans is modeled and an estimate of the relationship between benzene exposure and fraction metabolized in the bone marrow is obtained and is shown to be linear for the subjects studied.
Statistical analysis of Clewell et al. PBPK model of trichloroethylene kinetics.
  • F. Bois
  • Biology
    Environmental health perspectives
  • 2000
TLDR
A Bayesian statistical framework was used to combine previous information about the model parameters with the data likelihood, to yield posterior parameter distributions and the use of the hierarchical statistical model yielded estimates of both variability between experimental groups and uncertainty in TCE toxicokinetics.
Evaluation of Physiologically Based Pharmacokinetic Models in Risk Assessment: An Example with Perchloroethylene
TLDR
This case study with PCE demonstrates the danger of relying on parent chemical kinetic data to validate a model that will be used for the prediction of metabolism, and the closest predictions of the urinary excretion observed in these low-concentration exposures.
Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study
TLDR
An illustrative case study interprets biomarker data from eight adult males with controlled exposures to trichloroethylene as if the biomarkers were random samples from a large population with unknown exposure conditions to reconstructing population-scale exposures using Bayesian inference.
Sensitivity of physiologically based pharmacokinetic models to variation in model parameters: methylene chloride.
TLDR
Time-dependent sensitivity analysis can be used as an aid in the design of experiments to estimate parameters by predicting the experimental conditions and sampling points which will maximize parameter identifiability.
Population toxicokinetics of tetrachloroethylene
TLDR
This work modeled the distribution and metabolism of tetrachloroethylene in humans and derived statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979).
...
1
2
3
4
5
...