, 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.
;
;
