SKIN-CAD®: Pharmacokinetic Model for Transdermal Drug Delivery

Pharmacokinetic-pharmacodynamic (PK-PD) models for percutaneous absorption are useful in evaluating the clinical performance and optimizing the design of transdermal therapeutic systems [1, 2]. Diffusion models have been developed in order to analyze diffusivity and partitioning of drugs in the skin [3, 4]. However, there are few in silico approaches for predicting the clinical performance as well as the side effects following transdermal drug delivery. We have developed a simulation software, SKIN-CAD®, for in silico PK-PD evaluation of transdermal drug delivery [5]. This includes the diffusion models for drug release from matrix device and drug permeation across the skin, the compartment model for the body elimination and distribution and the pharmacodynamic model. SKIN-CAD® can also analyze the effects of binding and metabolism in the skin, iontophoretic application and uptake by dermal blood flow. The PK-PD simulation using SKIN-CAD® requires the model parameters such as the thickness of stratum corneum, diffusion and partition coefficients in the skin, distribution volumes and rate constants for the compartment model and pharmacodynamic parameters. The model parameters can be determined independently from in vitro skin permeation study and intravenous administration study and can also be obtained from various literatures. In this study, we propose a method for evaluating clinical performance of transdermal therapeutic systems by using SKIN-CAD® together with the model parameters under clinical conditions.