Preclinical program
Pharmacokinetics of drugs
(Supervisors: prof. MUDr. Ondřej Slanař, Ph.D.; Doc. PharmDr. Martin Šíma, Ph.D.; Mgr. Danica Michaličková, Ph.D.; MUDr. Nikolina Kutinová Canová, Ph.D., MUDr. Pavel Ryšánek, Ph.D.)
The scientific work is focused on the study of the influence of various factors on the pharmacokinetics of selected drugs. The aim of the research is to describe the influence of various technological formulations, physiological/pathological conditions of the gastrointestinal tract, or alternative routes of administration, as well as to examine the possibilities of predicting the pharmacokinetics in humans using the found relationships. Lymphatic absorption of drugs is also evaluated.
Therapeutic potential of candidate drugs in preclinical models of selected diseases
(Supervisors: MUDr. Nikolina Kutinová Canová, Ph.D.; Mgr. Danica Michaličková, Ph.D.; Doc. PharmDr. Martin Šíma, Ph.D.)
The scientific work is focused on investigation of therapeutic potential of antioxidants and other cytoprotective compounds in preclinical models of multiple sclerosis (experimental autoimmune encephalomyelitis), obesity, non-alcoholic steatohepatitis, diabetic neuropathy and dementia, rheumatoid arthritis, neonatal hypoxic-ischemic encephalopathy etc. The studies involve investigation of the potential pharmacological modulation of inflammation and oxidative stress, measurement and evaluation the effects on selected functions in vivo and in vitro.
Incorporation and controlled release of pharmacologically active substances from hydrogel and nanofibrous polymer carriers (in co-operation with the Institute of Macromolecular Chemistry AS CR)
(supervisors: RNDr. Jakub Širc, Ph.D.; prof. MUDr. Ondřej Slanař, Ph.D.)
The dissertation thesis will focus on the issue of incorporation of biologically and pharmacologically active substances into polymer carriers and their subsequent controlled release. Polymeric carriers can be a) materials whose primary function is controlled drug delivery (eg. hydrogel carrier for controlled release of drugs to the gastrointestinal tract, nanofibres for topical application of anticancer drugs), b) have different function in different medical applications and drug release significantly increases drug release their therapeutic efficacy (eg. hydrogel wound dressing, macroporous hydrogel scaffolds, tissue expanders). The research will deal with mechanisms influencing release kinetics of incorporated molecules and preparation of polymeric carriers according to different medical requirements. The dissertation focuses on the boundary between polymer, organic, and physical chemistry and pharmacology.
Mitochondrial dysfunction in schizophrenia
(Supervisor: Doc. PharmDr. Jana Rečková Hroudová, Ph.D.)
The scope of the study is focused on elucidation of the pathophysiological processes in schizophrenia. Effects of psychopharmaca on mitochondrial functions and on cell energy metabolism have not been sufficiently clarified. It is insufficiently clarified It is presumed that therapeutic and/or adverse effects of psychopharmaca are related to changes in mitochondrial functions. Based on this hypothesis, in vitro effects of selected psychotropic drugs will be studied. Activities of mitochondrial enzymes, ATP production, and formation of reactive oxygen species will be evaluated using different methods (e.g. spectrophotometry, fluorescence, high resolution respirometry).
The preclinical research will be followed by clinically oriented research and selected mitochondrial parameters will be evaluated in blood components of patients with schizophrenia. Selected mitochondrial parameters (citrate synthase activity and respiratory chain complexes, respiratory rate, ATP production) and changes in the monoaminergic system (serotonin uptake, monoamine oxidase activity) will be measured in the peripheral blood elements. Changes in selected genes encoding subunits of individual complexes will also be analyzed by real time PCR.
The aim of the study is to determine the role of changes in cellular energy in the pathophysiology of schizophrenia, to follow up the effect of antipsychotic treatment and to evaluate possibility of utilization of biochemical parameters measured in peripheral blood, as biological markers of this mental disorder.
Clinical program
Pharmacogenetics
(supervisor: Prof. MUDr. Ondřej Slanař, Ph.D.)
Research in clinical pharmacology focuses on the study of the effects of genetic variations in drug biotransformation and on genetic and non-genetic changes in pharmacokinetics, pharmacodynamics, tolerance and efficacy of drugs in humans.
Therapeutic drug monitoring
(supervisors: PharmDr. Jan Hartinger, Ph.D.; Doc. PharmDr. Martin Šíma, Ph.D.)
The research focuses on the identification of predictive factors for the efficacy and safety of pharmacotherapy with the aim of their potential use for individualization of treatment in clinical practice.