Studies of the pharmacokinetic profiles of drugs with focus on interactions with transport and biotransformation proteins

Group for study of drug resistance and drug interactions

Group for study of drug resistance and drug interactions (leader prof. Barbora Szotáková) focuses on drug resistance, mechanisms of its origin, and possibilities of its control. At present, the main topics include:

  • Metabolism of drugs, activity, and regulation of drug-metabolizing enzymes and their role in drug interactions and resistance
  • Metabolism, toxicity, and protective effects of natural substances/food supplements
  • Mechanisms of drug resistance in parasitic helminths
  • The fate of veterinary anthelmintics in the environment

The role of drug-metabolizing enzymes and the role of drug transporters in the development of drug resistance in helminths have been studied for a long time. Given that the prevalence of parasite resistance to common anthelmintics has increased dramatically, research into the mechanisms of resistance development is very important. Effective detoxification of anthelmintics may be one of the mechanisms of helminth resistance. The administration of anthelmintics is currently necessary to treat parasitoses. At the same time, however, these drugs pose a risk to the ecosystems they enter with the excrements of treated animals. A newer focus of the group is the study of the circulation of veterinary drugs in the environment.

Another area of interest is the study of metabolism, toxicity, and protective effects of biologically active substances in food supplements. Dietary supplements containing pharmacodynamically active substances of a natural origin are becoming more and more popular. Because they are generally considered safe, although their metabolism in humans is often not fully elucidated, they are often consumed in excessively high doses. This may lead to the induction or inhibition of certain biotransformation enzymes and transport proteins, affecting the pharmacokinetics of concomitantly or sequentially administered drugs. Therefore, the toxic or protective effects of biologically active substances (mono- and sesquiterpenes, flavonoids, prenylated flavonoids) in various model systems are studied.

Recently, it has been shown that epigenetic factors, including histone modifications, DNA methylation, and regulation by small non-coding RNAs, can also be involved in resistance. In this area, the group focuses mainly on the study of the regulation of detoxification enzymes by microRNAs, which can potentially also play a role in the mechanisms of resistance development.

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