INVESTIGATION OF ABSORPTION KINETICS BY THE PHASE PLANE METHOD

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.