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Parameter determination

Method of residuals

Values for all these parameters can be determined by first calculating A, B, , and . For this we can use the method of residuals (in a similar fashion to determining ka and kel for the one compartment model after oral administration). By definition is greater than then as t --> , e-*t --> 0 faster than e- * t. Therefore if the ratio / is large enough (greater than 5) the terminal data points will fall on the line

Cplate = B * e- * t

This equation is similar to the equation for the late plasma concentration values after oral administration with a one compartment model. This line will be linear if plotted on semi-log graph paper.

From the slope of this line a value of can be determined. The t1/2 calculated as 0.693/ is often called the biological half-life or terminal half-life. It is the half-life describing the terminal elimination of the drug from plasma. [For the one compartment model the biological half-life is equal to 0.693/kel].

Figure XIX-4, Semi-Log Plot of Cp Versus Time Showing Cplate Extrapolated Back to B

The difference between the Cplate values at early times and the actual data at early times is again termed the 'residual'

Residual = Cp - Cplate = A * e-*t

Figure XIX-5, Semi-Log Plot of Cp Versus Time Showing Residual Line and Line

From the slope of the residual line the value of can be calculated with the A read off the concentration axis. With A, B, , and calculated we can calculate the microconstants given the formulas.

; ;

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kel is:
k12 is:
k21 is:
V1 is:

This page was last modified: 12 February 2001

Copyright 2001 David W.A. Bourne

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