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Styrene_Inhalation

A model for a physiological based description of the inhalation pharmacokinetics of styrene in rats and humans based on the work of J.C. Ramsey and M.E. Andersen [(1984). Toxicol Appl Pharm. 73(1), 159-175.], developed by Neil Geisler (2006) as a final project for BIOEN 589, University of Washington.

Model number: 0196

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Description

   This model presents a the phramacokinetics of styrene inhalation
in rats and humans based on the 1984 paper by Ramsey and Andersen paper
(reference below). Four body compartments are considered: richly perfused tissue
(highly perfused), muscle (moderately perfused), fat (slowly perfused), and
liver, which includes metabolic consumption of styrene. Styrene is inhaled at a
given concentration for a specified time, then normal ventilation continues.
Parameters for rats and humans are included, and are listed in the code below
along with parameters for mice as provided in the paper.  Two plot pages, one
for rats and one for humans, are given to reflect identical traces plotted in
the paper.



Equations

Styrene Ventilation:

$\large Q_{alv}(C_{inh}-C_{alv})=Q_t(C_{art}-C_{vent})$

$\large N=\frac{C_{art}}{C_{ven}}$

$\large C_{art}=\frac{(Q_{alv} \cdot C_{inh} + Q_t \cdot C_{ven})}{(Q_t+\frac{Q_{alv}}{N})}$

$\large C_{art}=\frac{(Q_t \cdot C_{ven})}{Q_t+\frac{Q_{alv}}{N})}$

$\large C_{exh}=0.7 \cdot C_{alv}+0.3 \cdot C_{inh}$

Styrene uptake, release, and metabolism in the tissue:

$\large \frac{dA_i}{dt}=Q_t \cdot (C_{art}-C_{vi})$

$\large C_i=\frac{A_i}{V_i}$

$\large C_{vi}=\frac{C_i}{P_i}$

$\large \frac{dA_{met}}{dt}=\frac{V_{max} \cdot C_{vl}}{K_m+C_{vl}}$

$\large \frac{dA_l}{dt}=Ql \cdot (C_{art}-C_{vl})-\frac{dA_{met}}{dt}$

$\large C_{ven}= \frac{\Sigma(Q_i \cdot C_{vi})}{Q_t}$

The equations for this model may also be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.

References

  Andersen, J.C. and Ramsey, M.E., A physiologically based description of the inhalation
pharmacokinetics of styrene in rats and humans, 1984 Toxicol Appl Pharmacol, 73(1), 159-175.



None.

Key Terms

Administration, Oral, Animals, Gases, Humans, Injections, Intravenous, Kinetics, Liver metabolism, Lung metabolisim, Male, Models, Biological, Rats, Inbred Strains, Species Specificity, Styrene metabolism, Data, Respiratory system, Air-blood gas exchange, Publication

Model History

Get Model history in CVS.

Posted by: bej

Acknowledgements

Please cite www.physiome.org in any publication for which this software is used and send an email with the citation and, if possible, a PDF file of the paper to: staff@physiome.org.
Or send a copy to:
The National Simulation Resource, Director J. B. Bassingthwaighte, Department of Bioengineering, University of Washington, Seattle WA 98195-5061.