Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution.
To evaluate the kinetics of topically applied clobetasol-17-propionate (CP-17) in lesional and non-lesional psoriatic skin when released from a commercially available low-strength cream using in vivo dermal open-flow microperfusion (dOFM).



Twelve patients received Dermovate® cream (CP-17, 0.05%) on small lesional and non-lesional skin test sites for 14 days, once daily. On day 1 and 14, dOFM samples were continuously taken in the dermis for 24 h post-dose and analyzed by LC-MS/MS. Probe depths were assessed by 50 MHz ultrasound scanning.



Mixed-effects modelling identified skin condition, treatment duration and probe-depth as kinetics determining variables. The time- and depth-resolved intradermal data revealed (i) slower penetration of CP-17 into lesional than into non-lesional skin, (ii) normalized (faster) skin penetration after repeated dosing, and (iii) no CP-17 accumulation within the dermis independently of the skin condition.



Intradermal investigation of a highly lipophilic drug released from low-strength cream was successfully performed by using dOFM and timely and spatially, i.e., probe-depth dependent, resolved kinetic data were delivered. These data support the assumption that the thickened psoriatic stratum corneum might act as trap compartment which lowers the skin penetration rate for lipophilic topical drugs.
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
Manfred
M
Bodenlenz
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
Christian
C
Dragatin
Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Lisa
L
Liebenberger
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
Bernd
B
Tschapeller
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.|Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Beate
B
Boulgaropoulos
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
Thomas
T
Augustin
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
Reingard
R
Raml
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.
Christina
C
Gatschelhofer
Galderma R&D, Sophia Antipolis, France.
Nathalie
N
Wagner
Galderma R&D, Sophia Antipolis, France.
Khaled
K
Benkali
Galderma R&D, Sophia Antipolis, France.
Francois
F
Rony
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria.|Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Thomas
T
Pieber
HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010, Graz, Austria. healthca@joanneum.at.|Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria. healthca@joanneum.at.
Frank
F
Sinner
D000279:Administration, Cutaneous; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods; D002990:Clobetasol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D010477:Perfusion / Q000379:methods; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology; D053719:Tandem Mass Spectrometry / Q000379:methods
D002990:Clobetasol
dermal pharmacokinetics; lipophilic drug; open flow microperfusion; skin penetration; topical formulation