Skip to main content

Advertisement

Log in

Uncertainties in physiologically based pharmacokinetic models caused by several input parameters

  • ORIGINAL ARTICLE
  • Published:
International Archives of Occupational and Environmental Health Aims and scope Submit manuscript

Abstract

Objective: One of the problems in the application of physiologically based pharmacokinetic (PB-PK) models is that authors often use different input parameters, with unknown influence on the results. Differences in the simulation results obtained with various sets of parameters are examined herein. Method: Chemicals considered were perchloroethylene, toluene, and styrene. Simulations of alveolar concentrations, blood concentrations, and urinary metabolite excretions were performed for the three solvents. The input parameters discussed herein are physiological values, metabolic constants, and partition coefficients. The influence of metabolic constants and partition coefficients is studied by comparison of models against one another. Results: Metabolic parameters such as Vmax and K m varied considerably between authors. Tissue-gas partition coefficients, especially for the fat compartment, also differed according to the authors. Such differences in input parameter values proved to have a large influence on PB-PK model results and, therefore, increased their uncertainties. Uncertainties were much more significant in urinary metabolite concentration than in alveolar and blood concentration for chemicals that are poorly metabolized. On the other hand, uncertainties were more significant in alveolar and blood concentrations than in urinary metabolite excretions for chemicals that are well metabolized. Conclusion: Careful attention is necessary in the selection and/or citation of values from published data. The validity of PB-PK models should be simultaneously confirmed with both the blood and/or alveolar concentration and urinary metabolite concentrations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Author information

Authors and Affiliations

Authors

Additional information

Received: 22 May 1998 / Accepted: 25 March 1999

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jang, JY., Droz, P. & Chung, H. Uncertainties in physiologically based pharmacokinetic models caused by several input parameters. Int Arch Occup Environ Health 72, 247–254 (1999). https://doi.org/10.1007/s004200050368

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s004200050368

Navigation