Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution

Skin penetration of high-potent topical glucocorticoids and the role of the stratum corneum (SC) in psoriasis for the kinetics of such lipophilic drugs are unclear. We evaluated whether in vivo dermal open-flow microperfusion (dOFM) can provide the kinetics of topical clobetasol-17-propionate (CP-17) in lesional and non-lesional psoriatic skin when released from a commercial low-strength cream. Twelve patients received Dermoval® 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 collected from the dermis continuously for 24h post-dose and analyzed by LC-MS/MS. dOFM delivered quantifiable CP-17 concentration profiles and 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 psoriatic skin compared to non-lesional skin, (ii) normalized (faster) skin penetration after repeated dosing, and (iii) that CP-17 does not accumulate in the dermis independently of the skin condition. dOFM enabled the intradermal investigation of a lipophilic drug released from a low-strength cream and delivered timely and spatially resolved kinetic data. The data support the assumption that the thickened SC of psoriatic skin acts as trap compartment for lipophilic topical drugs.