Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling
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Bodenlenz, Manfred, Höfferer, Christian, Magnes, Christoph, Schaller, R., Schaupp, L., Feichtner, F., Ratzer, Maria, Pickl, Karin, Sinner, Frank, Wutte, A., Korsatko, S., Köhler, G., Legat, F.J., Benfeldt, E., Wright, Andrew, Neddermann, Daniel, Jung, Thomas and Pieber, Thomas R. (2012) Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling. European Journal of Pharmaceutics and Biopharmaceutics, 81 (3). pp. 635-641. ISSN 0939-6411
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 25hrs 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 hours 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 eight 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.
| Item Type: | Article |
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| Additional Information: | A paid open access option is available for this journal. |
| Keywords: | Open Flow Microperfusion, Psoriasis, topical, Skin penetration, pharmacokinetics, pharmacodynamics |
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| Date Deposited: | 13 Oct 2015 13:14 |
| Last Modified: | 13 Oct 2015 13:14 |
| URI: | https://oak.novartis.com/id/eprint/7311 |