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Method of residuals

Starting with the equation for Cp versus time

Equation IX-1 Cp versus Time after Oral Administration this can be written as Cp = A * e-kel * t - A * e-ka * t

where A =

Figure IX-1, Semi-log Plot of Cp versus Time Showing a Straight Line at Longer Time Using a JAVA aware browser you can create your own version of Figure IX-1. Plasma Concentration versus Time Plots

• •

Linear Semi-log

If one of the rate constants (ka or kel) is much larger than the other, the method works best if the difference is at least five times, then the faster differential will approach zero more

Semi-log Plot of Cp versus Time Showing Cplate. and Intercept then Cplate = A * e-kel * t and plotting Cplate versus time gives a straight line on semi-log graph paper. with a slope (ln) = -kel and intercept = A. If we plot Cp versus time on semi-log graph paper we will see that the slope will approach a straight line. Now therefore . Slope.quickly. The equation for this straight line portion can be obtained from the equation for Cp by setting the faster term (usually e-ka*t) to zero: Figure IX-2. and at later times can be ignored.

Table IX-1: Example Data for the Method of Residuals Time (hr) 0.Plotting the ln (Residual) versus time should give another straight line graph with a slope (ln) equal to .50 4.07 3.98 4.5 0.ka * t Figure IX-3. It can give quite accurate values of kel.80 3.07 .73 4. ka. A ln (Residual) = ln (A) .32 2.23 4.84 3.ka and the same intercept as before.00 1.69 Residual [Col3 .54 3. i.0 Plasma Concentration (mg/L) 1.70 0.62 Cp(late) (mg/L) 5.0 1.75 1. Semi-log Graph of Cp versus Time Showing Residual Line This is the method of residual or "feathering".25 0.19 0.e. and V/F if :i) One rate constant is at least five times larger than the other and ii) Both absorption and elimination are first order processes.23 0.98 3.Col2] (mg/L) 3.5 2.91 2.

0 4.3. Press the Cp(late) button to plot the line and calculate the residual values. Up to eleven (11) different data points can be entered instead of the example data provided. Press the Plot Residual button to plot the residual line. Leave fields empty if there are fewer than 11 data points in your data set. Second: Draw the Residual line by changing the intercept (A(k2)) and slope (k2) values.37 Cplate = 5.2 * t Residual = 5.5 * e 2.04 2.49 2.0 5.67 1. .0 3.5 * e 0.05 * t Figure IX-4. First: Draw the Cplate line by changing the intercept (A(k1)) and slope (k1) values. By trial and error best fit lines can be drawn and the parameters determined.0 7.04 1. Plot of Cp and Residual versus Time The objective of this panel is to illustrate the Method of Residuals for determining information about the drug absorption process.0 6.

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