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Pharmacokinetic Modeling to Simulate the Concentration-Time Profiles Following Dermal Application of Rivastigmine Patch

Nozaki, Sachiko and Yamaguchi, Masayuki and Lefevre, Gilbert (2016) Pharmacokinetic Modeling to Simulate the Concentration-Time Profiles Following Dermal Application of Rivastigmine Patch. Journal of Pharmaceutical Sciences. ISSN 00223549

Abstract

Rivastigmine is an inhibitor of acetyl- and butyryl-cholinesterases for symptomatic treatment of Alzheimer's Disease (AD) and Parkinson’s Disease Dementia (PDD) and is available as oral and transdermal patch formulations. A dermal absorption pharmacokinetic (PK) model was developed to simulate the concentration-time profile of rivastigmine to answer questions relative to the efficacy and safety risks following misuse of the patch (e.g. longer application than 24 hours, multiple patches applied at the same time, etc.). The model comprised two compartments (skin and blood) which was a combination of mechanistic dermal absorption model and a basic 1-compartment model. The initial values for the model were determined based on the physicochemical characteristics of rivastigmine as well as previously reported PK parameters following intravenous administration. The model was fitted to the clinical PK profiles following single application of rivastigmine patch to obtain model parameters for the final model. The final model was validated by confirming that the simulated concentration-time curves and PK parameters (Cmax and AUC) conformed to the observed values, and then was used to simulate the PK profiles of rivastigmine after off-label use. This work demonstrated that the mechanistic dermal PK model fitted the clinical data well and was able to simulate the PK profile after off-label use in order to assess the impact of non-compliance to treatment on PK profiles.

Item Type: Article
Date Deposited: 27 May 2016 23:45
Last Modified: 27 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/28134

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