Pharmacokinetic analysis of the FDA guidance for industry–‘Topical dermatologic corticosteroids: in vivo bioequivalence’

Abstract

The FDA (Food and Drug Administration) Guidance for Industry ‘Topical Dermatologic Corticosteroids: In vivo Bioequivalence’ describes two methods for evaluation of cutaneously applied corticosteroid formulations by measurement of the skin blanching response with a chromameter. The experimental options are: staggered application with synchronized removal or synchronized application with staggered removal. From the resulting response vs. time profiles, the areas under the effect curves (AUECs) are calculated and plotted as a function of the exposure time period to obtain dose/response-like relationships. If these experimental procedures are analyzed pharmacokinetically applying the Bateman equation and Fick's First Law of diffusion, several critical factors may be determined that need to be considered in order to avoid misinterpretation of the data. If solution-type preparations are investigated, the applied formulation volume should be the same on all application sites. In the case of suspension-type preparations, the applied drug dose is not critical. Moreover, it is essential to guarantee zero order kinetics during the application time periods, which may only be achieved with suspension-type preparations or a sufficiently high volume of solution-type preparations. If all these critical factors are taken care of, bioavailability factors (solutions) and enhancement factors (suspensions) may be calculated as the quotient of the AUECs of test and reference formulations.