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Wissenschaftliche Publikation

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

Publikation aus Health

DI Manfred Bodenlenz, Höfferer C., Mag. Dr. Christoph Magnes, DI Dr. Roland Schaller-Ammann, Schaupp L, DDI Dr. Franz Feichtner, Ratzer M, DIin Dr.in Karin Pickl, Priv.-Doz. DI Dr. Frank Sinner, Wutte A., Korsatko S., Köhler G., Legat F., Benfeldt E., Wright A., Neddermann D., Jung T., Univ.-Prof. Dr. Thomas Pieber,

European Journal of Pharmaceutics and Biopharmaceutics 81 (3):635-641., 2012

Abstract:

BACKGROUND:

Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.

METHODS:

Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis.

RESULTS:

dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1.

CONCLUSIONS:

Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting.