We have developed simulation software, SKIN-CADŽ, for in silico pharmacokinetic-pharmacodynamic (PK-PD) evaluation of transdermal drug delivery. SKIN-CADŽ includes the diffusion model for drug release from dissolved- or dispersed-type matrix device and permeation across the skin and the compartment model for distribution in and elimination from the whole body. SKIN-CADŽ can also analyze the effects of skin binding, skin metabolism, iontophoretic application and uptake by dermal blood flow. The PK-PD simulation using SKIN-CADŽ requires the model parameters such as the thickness of the stratum corneum, the diffusion and partition coefficients in the skin, and the distribution volume and the rate constants for compartment model. The model parameters can be determined from in vitro skin permeation experiment and intravenous administration study. The time courses of blood concentration and pharmacologic effect can be well predicted by numerical simulation together with the model parameters determined and the given clinical conditions. We propose a method for evaluating clinical performance of transdermal therapeutic systems by using SKIN-CADŽ.