a%HIA human intestinal absorption fraction, oral dose administration; Pe is human jejunal permeability [56]; log ^ apparent octanol-water partition coefficient; logí^, octanol-water partition coefficient; pKa are ionization constants, at 0.01 M ionic strength; charge profile: the order in which charges on molecules change as pH is raised by 2-10. For example, for terbutaline at pH < 8.67 (pKai), the main species in solution is a cation ( + ); for pH 8.67-10.12, a zwitterion exists ( ± ); between pH 10.12 and 11.32, an anion forms ( — ); and for pH > 11.32, the dianion predominates ( = ). The symbol > denotes transition in charge state when pH is increased. The fraction of the molecule in the uncharged form at pH 7.4 is represented by/„.

(a) Permeability and Lipophilicity

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