Transfer Mechanism of Ionic Drugs: Piroxicam as an agent facilitating proton transfer

Facilitated proton transfer may be of potential significance in pharmacokinetic and pharmacodynamic processes. Here, we show that the NSAID piroxicam and its N-and O-methylated derivatives act as ionophores for proton transfer across the H₂O/1,2-dichloroethane interface. Investigations by cyclic voltammetry showed that the proton transfer occurs by interfacial protonation of the ionophore. The dissociation constants of the three compounds in the organic phase were calculated by Matsuda's theory. With this particular transfer mechanism, the present study exemplifies how electrochemistry at a liquid/liquid interface can be applied to calculate the fundamental thermodynamic parameters related to the pharmacokinetic behavior of ionic drugs.