Cp_min Equation

Equation 26.2.1 Cp_min after Many Oral Doses

This can be further simplified if we assume that the subsequent doses are given after the plasma concentration has peaked and e^{-ka • τ} is close to zero. That is the next dose is given after the absorption phase is complete.

Figure 26.2.1 Plot Cp Versus Time after a Single Dose showing Possible Time of Second Dose

Cp_min then becomes:

Equation 26.2.2 Cp_min after Many Oral Doses - Version 2

The relationship between loading dose and maintenance dose and thus drug accumulation during multiple dose administration can be studied by looking at the ratio between the minimum concentration at steady state and the concentration one dosing interval,τ, after the first dose. [Assuming e^{-ka • τ} is close to zero].

Equation 26.2.3 Ratio Between Cp after First and Last Dose

Which can be simplified to give:-

Equation 26.2.4 Ratio Between Cp after First and Last Dose

This turns out to be the same equation as for the IV bolus. Therefore we can calculate a loading dose just as we did for an IV multiple dose regimen.

Equation 26.2.5 Loading Dose Equation

This equation holds if each dose is given after the absorption phase of the previous dose is complete.

We can further simplify Equation 26.2.2, if we assume that ka >> kel then (ka - kel) is approximatley equal to ka and ka/(ka - kel) is approximately equal to one.

Equation 26.2.6 Cp_min after Many Oral Doses - Version 3

Equation 26.2.6 is an even more extreme simplification. However, it can be very useful if we don't know the ka value but we can assume that absorption is reasonably fast. Equation 26.2.6 will tend to give concentrations that are lower than those obtained with the full equation (Equation 26.2.1). Thus any estimated fluctuation between Cp_min and Cp_max will be overestimated using the simplified equation.

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