Prediction of Plasma Concentration of GTS-21 in Hairless Rats Following Monolithic Transdermal Delivery.

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Abstract
The transdermal therapeutic systems (TTS) usually achieve constant plasma concentration for an extended period of time. This is because a sufficient drug stored in the device can keep the constant concentration on the surface of the stratum corneum during the system application. When the drug molecules are not enough to provide the constant surface concentration, the rate of drug penetration decreases with time because of decreased supply of the drug molecules from the delivery device. This paper has proposed an empirical simple approach to predict the plasma concentration for such a TTS. A novel compound, GTS-21, for Alzheimers' disease currently under development was used as a model drug. In vivo and in vitro experiments were carried out in hairless rats. The in vivo plasma concentration–time profile in hairless rats following the application of TTS well agreed with the predicted profile based on the skin pharmacokinetic model together with the model parameters determined from the in vitro experiment.