Estimation of blood concentration of drugs after topical application from in vitro skin permeation data. II. Approach by using diffusion model and compartment model.

Abstract

In order to estimate the in vivo behavior (e.g., blood concentration) of drugs on percutaneous absorption from in vitro permeation data using excised skin and pharmacokinetic parameters at intravenous administration, two models, a diffusion model and a compartment model with or without shunt transport, were established and applied to the in vitro and in vivo skin permeation data of nicorandil in hairless rats. When water was employed as a donor solvent (water treatment), the plasma concentration-time curve, which was calculated by means of the diffusion model, was similar to the observed values without introduction of shunt transport. In the case of propylene glycol treatment, on the other hand, the calculated plasma levels were not necessarily similar to the observed values, but it was found that the calculated values were better fitted to the observed values by introduction of shunt transport in the in vitro skin diffusion model. Similar results were obtained with the compartment model. These results suggest that both models may be useful to predict the plasma concentration after application of topical formulations. The characteristics and usefulness of these models were compared with those of the previously reported convolution method.