Leader of the research programme:
This research program focuses on elucidation if and how a biologically active substance is absorbed into the organism, transformed by the organism and whether it is not toxic within the range of therapeutic concentrations and no negative interactions with other concurrently administered substances are observed. Research program includes the following tasks: 1. Pharmacologic studies of proposed compounds; their metabolism and evaluation of drug interactions, preclinical modelling conditions in the animals that will closely replicate the clinical situation; 2. Pharmacogenetic implications of drug metabolism; 3. Cellular toxicity (induced by chemical and physical noxes) and chemopreventive effects and biosafety of substances studied. Initial step in the research plan is identification of a suitable means of administration into the organism, next is verification of pharmacokinetics linearity by testing dose dependence in series with various doses and finding the basic pharmacokinetic parameters using a suitable experimental model. Next, the substance distribution pattern will be investigated to detect its presence or absence in the most important tissues and organs of experimental model organisms. In the context of the Project, a rapid preclinical pharmacodynamic evaluation in animal models of human diseases will be used to confirm that an optimized lead acts on its intended molecular target as designed by the Project Team. Interactions between a tested substance and other substances at the level of metabolism will be performed to estimate the probability of unwanted drug-drug interactions. Concurrent with evaluation of substance metabolism, characterization of its potential for photodynamic therapy, chemoprotective /chemopreventive activities as well as toxic interactions will be performed on several levels, including biosafety.
Deliverables: 1. Pharmacokinetic and pharmacodynamic studies of compounds that will closely replicate the clinical situation and will be potentially used for registration studies; 2. Cellular toxicity of tested substances; 3. Chemoprotective and biosafety studies of tested substances; 4. Studies on toxicity and use of photosensitizers in photodynamic therapy. All deliverables will start from 2013 and will be published in the form of papers, research reports, patents and conference presentations.
Key methodological approaches: Genomics, proteomics, metabolomics, bioanalytics, in vivo and in vivo toxicology and metabolism