Determining bioequivalence of topical dermatological drug products by tape-stripping.

The maximum level of drug in the stratum corneum (C(max)) and the area under the curve of drug level in the stratum corneum versus time (AUC) have been proposed as metrics for assessing bioequivalence of topical drugs. These metrics, which require that concentrations be measured at eight or more times, were developed for drugs that are absorbed into the bloodstream, and are less appropriate for topical drugs. Concentrations of topical drugs are measured by tape-stripping, and it is difficult to make a large number of precise measurements due to the limited amount of available skin. We present a new method (the two-time method) for assessing bioequivalence of topical drugs. The method involves some modifications to standard tape-stripping methodology, designed to reduce the variability in measured drug levels. Perhaps most importantly, drug levels are measured at only two times, one during the uptake phase and one during the clearance phase. Measuring concentrations at only two times allows replicate measurements to be made, which increases efficiency. We compared the performance of the two-time method with a standard method through a simulation study that uses a model based on real data. When two drugs are in fact bioequivalent, the two-time method requires only 20 subjects to achieve the efficiency of a standard study with 50 subjects. In a situation in which two drugs are bioinequivalent, the two-time method requires only 30 subjects to achieve the efficiency of a standard study with 100 subjects.