Figure XV-2, Plot Cp Versus Time after a Single Dose showing Possible Time of Second Dose
This can be further simplified if we assume that the subsequent doses are given after the plasma concentration has peaked and e-ka * t is close to zero. That is the next dose is given after the absorption phase is complete.
Cpmin then becomes:-
Equation XV-4 Cp Equation Simplified
Equation XV-5 Cp Equation Simplified Again
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 (t) after the first dose.
Which can be simplified to give:-
Equation XV-6 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 XV-7 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 XV-4, if we assume that ka >> kel
then (ka - kel) approximatley equal to ka and thus approximately = 1.
Equation XV-8 Cp after Many Oral Doses (Uniform Dose and Interval)
Equation 71 is an even more extreme simplification. However, it can be very useful if we don't know what the ka value is but can assume that absorption is reasonably fast. Equation 71 will tend to give concentrations that are lower than those obtained with the full equation (Equation 67). Thus any estimated fluctuation between Cpmin and Cpmax will be overestimated using the simplified equation.
Copyright 2001 David W.A. Bourne