TY - JOUR
T1 - Assessment of skin permeability to topically applied drugs by skin impedance and admittance
AU - Schwingenschuh, Simon
AU - Scharfetter, Hermann
AU - Martinsen, Orjan G.
AU - Boulgaropoulos, Beate
AU - Augustin, Thomas
AU - Tiffner, Katrin I.
AU - Dragatin, Christian
AU - Raml, Reingard
AU - Hoefferer, Christian
AU - Prandl, Eva Christina
AU - Sinner, Frank
AU - Hajnsek, Martin
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Objective: Pharmacokinetic and pharmacodynamic studies of topically applied drugs are commonly performed by sampling of interstitial fluid with dermal open flow microperfusion and subsequent analysis of the samples. However, the reliability of results from the measured concentration-time profile of the penetrating drug suffers from highly variable skin permeability to topically applied drugs that is mainly caused by inter- and intra-subject variations of the stratum corneum. Thus, statistically significant results can only be achieved by performing high numbers of experiments. To reduce the expenditures needed for such high experiment numbers we aimed to assess the correlation between skin permeability and skin impedance/skin admittance. Approach: We performed an ex vivo drug penetration study with human skin, based on the hypothesis that inter-subject variations of the respective concentration-time profiles can be correlated with variations of the passive electrical properties of the skin. Therefore, skin impedance and skin admittance were related to the skin permeability to the model drug Clobetasol-17-proprionate. Main results: The measured low frequency skin impedance and the skin admittance correlated linearly with the drug concentration-time profiles from dermal sampling. Significance: Skin permeability can be assessed by measuring the passive electrical properties of the skin, which enables correction of skin permeability variations. This allows reduction of experiment numbers in future pharmacokinetic and pharmacodynamic studies with human skin ex vivo and in vivo and leads to diminished study costs.
AB - Objective: Pharmacokinetic and pharmacodynamic studies of topically applied drugs are commonly performed by sampling of interstitial fluid with dermal open flow microperfusion and subsequent analysis of the samples. However, the reliability of results from the measured concentration-time profile of the penetrating drug suffers from highly variable skin permeability to topically applied drugs that is mainly caused by inter- and intra-subject variations of the stratum corneum. Thus, statistically significant results can only be achieved by performing high numbers of experiments. To reduce the expenditures needed for such high experiment numbers we aimed to assess the correlation between skin permeability and skin impedance/skin admittance. Approach: We performed an ex vivo drug penetration study with human skin, based on the hypothesis that inter-subject variations of the respective concentration-time profiles can be correlated with variations of the passive electrical properties of the skin. Therefore, skin impedance and skin admittance were related to the skin permeability to the model drug Clobetasol-17-proprionate. Main results: The measured low frequency skin impedance and the skin admittance correlated linearly with the drug concentration-time profiles from dermal sampling. Significance: Skin permeability can be assessed by measuring the passive electrical properties of the skin, which enables correction of skin permeability variations. This allows reduction of experiment numbers in future pharmacokinetic and pharmacodynamic studies with human skin ex vivo and in vivo and leads to diminished study costs.
KW - open flow microperfusion
KW - pharmacodynamics
KW - pharmacokinetics
KW - skin admittance
KW - skin impedance
KW - skin penetration
KW - topical drugs
UR - http://www.scopus.com/inward/record.url?scp=85034748696&partnerID=8YFLogxK
U2 - 10.1088/1361-6579/aa904e
DO - 10.1088/1361-6579/aa904e
M3 - Article
C2 - 28967873
AN - SCOPUS:85034748696
SN - 0967-3334
VL - 38
SP - N138-N150
JO - Physiological Measurement
JF - Physiological Measurement
IS - 11
ER -