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Figure 11.2.1 Excel™ Spreadsheet Illustrating a best-fit to a straight line
Figure 11.2.2 Excel™ Spreadsheet Illustrating a best-fit to a one Compartment Model - IV Bolus
Figure 11.2.3 Excel™ Spreadsheet Illustrating a best-fit to a one Compartment Model - Oral
You can download each of these worksheets (actually all in the same file) and try your own version of optimization. Change the parameter values and watch the value for the objective function, WSS, change. With a little 'fiddling' you should be able to get close to a best-fit. Try the straight line example first.
Note, in contrast to your adjusting the parameter values and seeing the effect the digital computer does this best-fit optimization blind-folded. Before we move onto how the digital computer does this magic lets look briefly at another type of computer.
My first computer assisted pharmacokinetic modeling was done with an analog computer, similar to the EAI 680, but from memory smaller.
Figure 11.2.4 Patch Panel EAI 680 Analog Computer
An image from the Computer Museum, University of Amsterdam, The Netherlands website.
The model was constructed by moving the patch cords, labelled arrows, in the figure. Adjustment of the potentiometers was equivalent to adjusting the rate constants of the model. Output was to an oscilloscope. Optimization was performed by 'twiddling' with the potentiometers and watching the oscilloscope for a match with data. Great fun!
Visit the Computer Museum, University of Amsterdam, The Netherlands website to see more information about analog and other computers. The 'Play-Hookey.com' website also has some interesting information about how analog computers work.
Numerical integration as the speed of light...electron.
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