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Elimination Rate Constant, kel

The elimination rate constant (abbreviated as kel, k10, and sometimes ke) is the first order rate constant describing drug elimination from the body. This is an overall elimination rate constant describing removal of the drug by all elimination processes including excretion and metabolism. Metabolites are different chemical entities and have their own elimination rate constant.

The elimination rate constant is the proportionality constant relating the rate of change drug concentration and concentration OR the rate of elimination of the drug and the amount of drug remaining to be eliminated.

Defining Equations:

Table 5.6.1 Equations Defining kel

dCp/dt versus Cp dX/dt versus X
Equation 5.6.1 Rate of Change of Cp versus Cp Equation 5.6.2 Elimination Rate versus Amount Remaining, X

Units:

By inspection of Equations 5.61. or 5.6.2 it can be seen that the units for kel are time-1, for example hr-1, min-1, or day-1. In both equations the rate expression is divided by Cp or X, respectively to provide units for kel. Thus:

Table 5.6.2 Units for kel

Units for kel from Cp Units for kel from X
Units for kel from Equation 5.6.1 Units for kel from Equation 5.6.2

Determining Values of kel:

From the integrated equation presented on the previous page:

Ln(Cp) versus time

Equation 5.6.3 Ln(Cp) versus time

Plotting ln(Cp) values versus t, time should result in a straight line with a slope equal to -kel, thus kel can be calculated as:

kel equation

Equation 5.6.4 kel from -slope

Thus with two value for Cp and time data a value for kel can be determined. With more than two Cp - time data points it is possible to plot the data on semi-log graph paper and draw a 'best-fit' line through the data points. This plot is shown on the previous page. The best answer for kel can be calculated by taking points at either end of the 'best-fit' line. This approach has been covered in more detail earlier in Chapter 2.

Note: We should now distinguish between the elimination rate and the elimination rate constant. The rate (tangent or slope, dCp/dt) changes as the concentration changes, however, for a linear model the rate constant (kel) is constant, it does not change.


Table 5.6.3. Example Values for Elimination Rate Constant1

Drug kel, hr-1
Acetaminophen0.28
Diazepam0.021
Digoxin0.017
Gentamicin0.35
Lidocaine0.43
Theophylline0.063

1 Ritschel, W.A. 1980 Handbook of Basic Pharmacokinetics, 2nd ed., Drug Intelligence Publications, p 413-426.


References

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Copyright 2001-3 David W. A. Bourne (david@boomer.org)


This file was last modified: Wednesday 26 May 2010 at 07:43 PM