Purpose. To develop a simple approach for investigating absorption kin
etics, which does not require modeling assumptions or intravenous data
. Methods. The concentration (C) -time (t) data are plotted as a phase
plane plot (dC/dt versus C). Errorless C,t data were generated from o
ne and two compartment models employing first-order, zero-order and Mi
chaelis-Menten input kinetics, and the phase plane plots were construc
ted. A simple test based on the ratio of slopes of the separate linear
regression analyses of absorption and elimination data of the phase p
lane plot is proposed to justify or not the presence of zero-order inp
ut kinetics. Errant data were used to assess the performance of the te
st developed. Literature data of theophylline and nitroglycerin formul
ations were analyzed using the phase plane plot. Input rate-time profi
les were constructed for one compartment model drugs utilizing the dat
a of the phase plane plot. Results. The geometric forms of the phase p
lane plots derived from the errorless data of the various pharmacokine
tic models were found to be indicative of the absorption kinetics. Ver
y good results were obtained when the test for the discernment of abso
rption kinetics was applied to errant data. Zero-order absorption kine
tics were justified (i) for the transdermal absorption of nitroglyceri
n and (ii) only for a certain period of time, for the gastrointestinal
absorption of theophylline. Conclusions. Investigation of absorption
kinetics can be accomplished with the phase plane method. The cumulati
ve character of the classical percent absorbed versus time plots can b
e misleading in justifying the presence of zero-order input kinetics.