Transdermal imiquimod and LPS challenge on pharmacokinetics

Background: The Department of Clinical Pharmacology (Medical University of Vienna) is conducting a study to examine the dynamics of skin inflammation and antibiotic distribution. This research is centered around artificially induced skin inflammation in healthy individuals, which is then compared to natural inflammatory conditions in patients with skin infections. The study`s approach provides an opportunity to observe the body`s response to different states of skin inflammation and infection. Aims: The primary objective of the study is to develop a reliable method for inducing skin inflammation in a controlled laboratory environment. This is achieved through the application of substances such as imiquimod, a cream known to cause irritation, or LPS, a bacterial component. The secondary objective focuses on the pharmacokinetics of azithromycin, specifically its transportation and distribution in various skin states including healthy, artificially inflamed, and naturally infected skin. Understanding the behavior of antibiotics in these different conditions is crucial for effective treatment strategies in skin infections. Methods: The research is structured into three parts: Part 0: In this phase, healthy volunteers are subjected to skin inflammation using imiquimod and LPS. The focus here is on assessing the safety of these methods and their effectiveness in inducing inflammation. Additionally, technologies like imaging-based mobile phone applications are utilized for objective inflammation measurement. Part A: The study then progresses to analyze the pharmacokinetics of azithromycin in artificially inflamed skin. Following the induction of inflammation, volunteers are administered azithromycin, and its concentration is measured in both the inflamed and normal skin using microdialysis (a technique to measure tissue concentrations). This part aims to provide insights into how drugs are absorbed and act in inflamed tissue compared to normal tissue. Part B: The final part involves patients with real skin infections. Here, the concentration of azithromycin in naturally infected and healthy skin is measured, mirroring the methodology of Part A but in the context of natural inflammation. The study utilizes a variety of methods including clinical assessments, biopsies, blood sample analyses, and microdialysis to offer a comprehensive understanding of skin response and drug dynamics in different states of inflammation and infection. By comparing artificially induced inflammation with natural skin conditions, the study aims to contribute valuable insights into skin pharmacology and immunology, potentially informing more effective treatment approaches for skin diseases.