Equation

This term is defined as the area under the plasma concentration versus time curve during the dosing interval at steady state divided by the dosing interval.

Thus:

Equation 26.3.1 Average Cp for a Dosing Interval at Steady State

Figure 26.3.1 Plot of Cp versus Time after Multiple Oral Administration showing AUC at Steady State

Since,

Equation 26.3.2 AUC Equation

from the equations developed during the Wagner-Nelson derivation or from the clearance (kel • V) equation.

Equation 26.3.3 Average Cp for a Dosing Interval at Steady State

Note that the AUC during one dosing interval at steady state is the same as the AUC from zero to infinity after one single dose.

Also, an interesting result of this equation is that we get the same average plasma concentration whether the dose is given as a single dose every dosing interval, τ, or is subdivided into shorter dosing intervals. For example 300 mg every 12 hours will give the same average plasma concentration as 100 mg every 4 hours. However, the difference between the maximum and minimum plasma concentration will be larger with less frequent dosing.

An Example - Part 1

We could now calculate the loading dose

To get some idea of the fluctuations in plasma concentration we could calculate the Cpmin value.

Assuming that ka >> kel and that e^{-ka • τ} --> 0, using Equation 26.2.6.

Therefore the plasma concentration would probably fluctuate between 7 and 23 mg/L (very approximate) with an average concentration of about 15 mg/L. [23 = 15 + (15 - 7), i.e. high = average + (average - low), very approximate!].

Figure 26.3.2 Figure Illustrating Cp_max, Cp_min and Cp(average)

An Example - Part 2

The would be the same

Thus the plasma concentration would fluctuate between about 10.4 to 20 with an average of 15 mg/L.

Next Page

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