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Uncertainties in Pharmacokinetic Modeling for Perchloroethylene: II. Comparison of Model Predictions with Data for a Variety of Different Parameters

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  • Dale Hattis
  • Paul White
  • Paul Koch

Abstract

In this paper we compare expectations derived from 10 different human physiologically based pharmacokinetic models for perchloroethylene with data on absorption via inhalation, and concentrations in alveolar air and venous blood. Our most interesting finding is that essentially all of the models show a time pattern of departures of predictions of air and blood levels relative to experimental data that might be corrected by more sophisticated model structures incorporating either (a) heterogeneity of the fat compartment (with respect to either perfusion or partition coefficients or both) or (b) intertissue diffusion of perchloroethylene between the fat and muscle/VRG groups. Similar types of corrections have recently been proposed to reduce analogous anomalies in the fits of pharmacokinetic models to the data for several volatile anesthetics.(17‐20) A second finding is that models incorporating resting values for alveolar ventilation in the region of 5.4 L/min seemed to be most compatible with the most reliable set of perchloroethylene uptake data.

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  • Dale Hattis & Paul White & Paul Koch, 1993. "Uncertainties in Pharmacokinetic Modeling for Perchloroethylene: II. Comparison of Model Predictions with Data for a Variety of Different Parameters," Risk Analysis, John Wiley & Sons, vol. 13(6), pages 599-610, December.
    • Handle: RePEc:wly:riskan:v:13:y:1993:i:6:p:599-610
    DOI: 10.1111/j.1539-6924.1993.tb01322.x
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    References listed on IDEAS

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    1. Kenneth T. Bogen & Thomas E. McKone, 1988. "Linking Indoor Air and Pharmacokinetic Models to Assess Tetrachloroethylene Risk," Risk Analysis, John Wiley & Sons, vol. 8(4), pages 509-520, December.
    2. Dale Hattis & Paul White & Laura Marmorstein & Paul Koch, 1990. "Uncertainties in Pharmacokinetic Modeling for Perchloroethylene. I. Comparison of Model Structure, Parameters, and Predictions for Low‐Dose Metabolism Rates for Models Derived by Different Authors," Risk Analysis, John Wiley & Sons, vol. 10(3), pages 449-458, September.
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    Cited by:

    1. Dale Hattis & Gary Ginsberg & Bob Sonawane & Susan Smolenski & Abel Russ & Mary Kozlak & Rob Goble, 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 Analysis, John Wiley & Sons, vol. 23(1), pages 117-142, February.
    2. Leona H. Clark & R. Woodrow Setzer & Hugh A. Barton, 2004. "Framework for Evaluation of Physiologically‐Based Pharmacokinetic Models for Use in Safety or Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 24(6), pages 1697-1717, December.
    3. Kimberly M. Thompson & John S. Evans, 1997. "The Value of Improved National Exposure Information for Perchloroethylene (Perc): A Case Study for Dry Cleaners," Risk Analysis, John Wiley & Sons, vol. 17(2), pages 253-271, April.

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