Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.
Eur J Pharm Biopharm
; 81(3): 635-41, 2012 Aug.
Article
in En
| MEDLINE
| ID: mdl-22554768
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Psoriasis
/
Tumor Necrosis Factor-alpha
/
Microdialysis
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Eur J Pharm Biopharm
Journal subject:
FARMACIA
/
FARMACOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
Austria