This thesis summarizes (i) the design of novel sampling devices for continuous sampling from the skin and subcutaneous tissue, (ii) the evaluation of the devices at the clinic on volunteers and patients and (iii) the utilization of the devices in clinical pharmaceutical trials proving the devices’ utility for clinical pharmacokinetics and -dynamics (PK-PD) as well as topical bioequivalence. The thesis has been motivated by the needs in basic medical research and pharmaceutical industry for an alternative clinical sampling method which can provide direct access to human tissues for the investigation of a wider range of biomolecules and drugs than is currently feasible by state-of-the-art microdialysis. The work focused on device applicability in the field of dermatology as the requirements in dermatological PK, PD and bioequivalence trials were most challenging considering the physico-chemical properties of the topical drugs designed for skin penetration and considering the specific needs of efficient and reliable clinical test settings. Consequently, this led to CE-certified medical devices for open-flow microperfusion (OFM) and specifically for dermal open-flow microperfusion (dOFM) which proved to be safe, tolerable, precise and versatile in clinical research supporting very long and data-rich multi-probe research protocols on virtually any molecule of interest in the interstitial fluid space. The devices enabled a number of clinical studies on healthy volunteers and patients providing important insights into the barrier function of psoriatic skin for topical drug penetration, on biomarkers in psoriasis, on therapeutic antibody concentrations within the skin as well as topical bioequivalence of generic drugs. This thesis summarizes the peer-reviewed publications in renowned medical and pharmaceutical journals along with information on the device design and discusses the vast opportunities this novel clinical research tool will provide in future pharmaceutical research.
|Qualifikation||Doktor der Technik|
|Betreuer/-in / Berater/-in|
|Publikationsstatus||Veröffentlicht - 10 Aug 2017|