title: Tissue binding affects the kinetics of theophylline diffusion through the stratum corneum barrier layer of skin.
abstract: 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.
authors.affiliation: Health Effects Laboratory, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. HFrasch@cdc.gov
authors.forename: H Frederick
authors.initials: HF
authors.lastname: Frasch
authors.forename: Ana M
authors.initials: AM
authors.lastname: Barbero
authors.forename: Justin M
authors.initials: JM
authors.lastname: Hettick
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Nitsche
mesh_terms: D000279:Administration, Cutaneous; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D016014:Linear Models; D008954:Models, Biological; D010539:Permeability; D011485:Protein Binding; D012869:Skin Absorption; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D013806:Theophylline