Most of the time the drug absorption process is linear or a 1st order process. At times it is zero order or constant, however.
Generally most drugs have a much faster absorption compared to clearance. The terminal phase will thus be dictated by clearance and not absorption. If this is not the case, then this is termed “flip-flop kinetics” and this is less common but does happen.
Moment method for estimating absorption (ka)
If the system is linear and mamillary then you can use the moment method to estimate absorption (ka). Note, the moment method can be used for 1-, 2-, etc. compartmental systems. This is done using mean residence times (MRT).
MRToral = MRT po
MRTpo = 1/ka + 1/Clearance/Volume
MRTintravenous = MRTiv
MRTiv = 1/Clearance/Volume
MRTiv-MRTpo = 1/ka
ka = 1/(MRTiv-MRTpo)
Wagner-Nelson Method – A Mass-Balance Approach
If zero order: 1-FA vs t is linear
if ln(1-FA) vs t is linear, it is 1st order absorption
Area-Function Method for Estimating ka (for linear, stationary systems)
Deconvolve absorption from disposition
Input process G(t) and Civ(t) is the disposition function
Cpo(t) is the time course of drug after oral administration
Cpo(s) = Civ(s)+G(s)
G(s) = Cpo(s)/Civ(s)
If you take the Laplace of the entire system and divide out what happens with IV, then we are left with oral.
The distribution and elimination process is the exact same for iv and oral. The only difference between the two is the input process. That is why when we divide out the iv process, we are left with the input process.
Then we can use that information for getting ka or ko.
So you can check ka(t) and see if it is constant or exponentially declining, etc. If it is constant, then it is a zero order system. if it is linear, then it is a first-order (for ln(y-axis)). For linear y, it would be exponentially declining.