Variability of Skin Pharmacokinetic Data: Insights from a Topical Bioequivalence Study Using Dermal Open Flow Microperfusion

Publikation aus Health
Biomedizinisches Gewebemonitoring, Datenanalyse und statistische Modellierung

Manfred Bodenlenz, Thomas Augustin , Thomas Birngruber, Katrin I. Tiffner , Simon Schwingenschuh, Sam G. Raney, Elena Rantou, Frank Sinner

Pharmaceutical Research , 9/2020


Purpose: Dermal open flow microperfusion (dOFM) has previously demonstrated its utility to assess the bioequivalence (BE) of topical drug products in a clinical study. We aimed to characterize the sources of variability in the dermal pharmacokinetic data from that study.


Methods: Exploratory statistical analyses were performed with multivariate data from a clinical dOFM-study in 20 healthy adults evaluating the BE, or lack thereof, of Austrian test (T) and U.S. reference (R) acyclovir cream, 5% products.


Results: The overall variability of logAUC values (CV: 39% for R and 45% for T) was dominated by inter-subject variability (R: 82%, T: 91%) which correlated best with the subject's skin conductance. Intra-subject variability was 18% (R) and 9% (T) of the overall variability; skin treatment sites or methodological factors did not significantly contribute to that variability.


Conclusions: Inter-subject variability was the major component of overall variability for acyclovir, and treatment site location did not significantly influence intra-subject variability. These results support a dOFM BE study design with T and R products assessed simultaneously on the same subject, where T and R treatment sites do not necessarily need to be next to each other. Localized variation in skin microstructure may be primarily responsible for intra-subject variability.

Keywords: Topical bioequivalence; acyclovir; dermal open flow microperfusion; inter- and intra-subject variability; microdialysis; skin pharmacokinetics.