Using Pharmacokinetic Parameters from in vitro Permeation Test Data for Predicting Multiple-Dose Penetration Profiles.

Abstract

Introduction: Several complex mathematical models have been developed using in vitro permeation test (IVPT) data to characterize percutaneous absorption. A less complicated approach, using basic pharmacokinetic parameters on IVPT data, is proposed here to predict skin barrier content and permeation kinetics following multiple-dose applications.

Methods: Published and archived data from the authors' files are used to define and test a proposed model using standard single-compartment pharmacokinetic parameters and to provide insight into percutaneous absorption profiles and skin barrier content.

Results: Pharmacokinetic parameters are derived and shown for a selection of diverse drugs from their IVPT data, which are then used to predict multiple-dose absorption kinetics. Flux profiles and skin barrier content are calculated and shown for periods of 7-30 days with 6-, 12-, and 24-h dosing intervals.

Conclusion: The model presented here allows one to predict the rate and extent of drug absorption over any number of dosing periods per day and across multiple days. This information may not only provide a new outlook on formulation selection or dosing regimens, but may also allow for estimation of skin or systemic levels of exposure to chemicals following multiple sequential topical dose applications.