A biophysically based dermatopharmacokinetic compartment model for quantifying percutaneous penetration and absorption of topically applied agents. I. Theory.
We present a general comprehensive mathematical model to stimulate and predict percutaneous absorption and subsequent disposition of chemicals in vivo that is chiefly based on biophysical parameters estimated or measured with in vitro and ex vivo perfused skin preparations. Current physicochemical principles of drug diffusion and partitioning across the skin barrier, solute and solvent concentration dynamics, the influence of solute and solvent on the stratum corneum barrier, and dynamic vascular perfusion effects are integrated in this model. Such a comprehensive approach is necessary to achieve optimal biological relevance in a quantitative model of percutaneous absorption, particularly when a chemical is applied as a binary (solute and solvent) or more complex formulation or chemical mixture. The proposed model should have applications in (a) designing drugs and permeation enhancers for passive or active (e.g., electrically assisted) transdermal drug delivery, (b) assessing the systemic exposure of topical drugs used in dermatology, and (c) integration into other mathematical models being developed to assess the risk after topical exposure to mixtures of environmental pollutants. We also have included experimental data to provide a preliminary illustration of the performance of the model.
Williams
P L
PL
Cutaneous Pharmacology and Toxicology Center, North Carolina State University, Raleigh 27606, USA.
Riviere
J E
JE
D000287:Administration, Topical; D000818:Animals; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D010539:Permeability; D010599:Pharmacokinetics; D019800:Phenol; D010636:Phenols / Q000493:pharmacokinetics*; D012869:Skin Absorption; D013552:Swine; D013997:Time Factors
D010636:Phenols; D019800:Phenol