Significance of viable skin layers in percutaneous permeation and its implication in mathematical models: theoretical consideration based on parameters for betamethasone 17-valerate.
The role of viable skin layers (viable epidermis and dermis) is examined by the three-layer model using parameter values for betamethasone 17-valerate. The mathematical three-layer diffusion model indicates that the lag time and half-life after vehicle removal in epidermis and split-thickness skin are longer than those in stratum corneum without viable layers, even if drug flux at steady-state is minimally altered. The theoretical values of the lag time and half-life predicted for epidermis and split-thickness-skin samples are compatible with the values observed in another in vitro study. The results predicted by the three-layer model indicate that the simplified model (single-layer or compartment model), which regards the whole skin as one diffusion layer or one compartment, may be warranted because all three skin layers have the same half-life after vehicle removal. The parameters used in the simplified model are estimated from some of the following values directly obtainable in the experiment: flux from skin and amount in the whole skin at steady-state, lag time, and drug concentration or amount maintained to be unchanged in the donor site. However, the simplified model often cannot resolve some discrepancy between the data and model (e.g., the ratio of the half-life to lag time) even if the data may be explained by the three-layer model.
Kubota
K
K
Department of Dermatology, University of California, School of Medicine, San Francisco 94143-0989.
Maibach
H I
HI
D001624:Betamethasone Valerate / Q000493:pharmacokinetics*; D006207:Half-Life; D008433:Mathematics; D008954:Models, Biological; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*
D001624:Betamethasone Valerate