Tissue binding affects the kinetics of theophylline diffusion through the stratum corneum barrier layer of skin.

New data sets on both (i) equilibrium theophylline (TH) partitioning/binding in stratum corneum and (ii) transient TH diffusion through human epidermis are explained by an extended partition-diffusion model with reversible binding. Data conform to a linear binding isotherm within the tested concentration range (0-2000 μg/mL) with an equilibrium ratio of bound-to-free solute of approximately 1.4. The permeability coefficient for TH is 4.86 × 10(-5) cm/h, and the lag time is 20.1 h. Binding occurs as a slow process, significantly affecting the kinetics of dermal penetration.