Microdialysis sampling and the clinical determination of topical dermal bioequivalence

Abstract

Our objective was to determine whether the degree of variability associated with dermal microdialysis allows its practical application to determinations of bioequivalence of topically applied agents with a reasonable number of subjects. A statistical review of literature data was conducted to estimate the variances associated with subject-to-subject variability and the probe-to-probe variability within the subjects. In order to successfully utilise dermal microdialysis to establish bioequivalence of topically applied agents, particular care must be applied to study design. Due to the inherent variability between subjects, to maintain subject numbers at reasonable levels, each subject should act as their own control, thus removing the element of subject-to-subject variability from calculations of sample sizes. It is also recommended that measurements are made in duplicate in each subject to reduce the element of variability further. It is then possible to demonstrate, within 80–125% confidence limits and a subject population of approximately 20, that two formulations are bioequivalent.