Transfer of the experimental methodology described in the FDA guidance for corticosteroid bioequivalence testing to pharmacodynamic effects caused by nicotinates.

BACKGROUND

The measurement of the pharmacodynamic response allows the noninvasive quantification of cutaneous drug penetration.

AIMS

The objective of this study was to investigate whether the experimental methods described in the US Food and Drug Administration Guidance for Industry "Topical Dermatologic Corticosteroids: In vivo Bioequivalence" may be transferred to other response parameters such as skin redness and surface temperature.

METHODS

Drug penetration experiments with methyl nicotinate in two different lipophilic vehicles were performed according to the FDA guidance for corticosteroid bioequivalence testing measuring the cutaneous erythema and skin temperature response.

RESULTS

The guidance methodology was transferred to the response parameters redness and temperature. Bioequivalence testing was feasible with these response parameters.

CONCLUSIONS

An open one-compartment model could only be confirmed for skin redness data by a compartmental analysis of response vs. time profiles. The obtained temperature data can neither be described by an open one-compartment nor by a two-compartment model. A correlation between skin color and skin surface temperature could not be found.