Poslední změna: 19.07. 2019
LivPharm - Liver Pharmacology
The objective is to study liver pharmacodynamics and pharmacokinetics of actual or potential drugs. We focus on executive and regulatory mechanisms of bile production and secretion (enzymes and transporting proteins) and their impairment by various liver diseases. Modulation of these mechanisms exerts significant physiological and pathophysiological consequences including changes in elimination of drugs. Consequent variability in PK/PD of co-administered agents may complicate therapeutic outcomes. Our purpose is therefore to study such changes and to introduce appropriate prophylactic and therapeutic measures. In particular we are working on nonalcoholic fatty liver disease, liver regeneration and cholestatic liver disorders characterized by impaired bile secretion due to extrahepatic biliary obstruction or due to intrahepatic influence of toxic insult like bacterial LPS or ethinylestradiol. Using animals and cellular models of these pathophysiological situations, we study protective effects of drugs modifying activity of PXR, CAR and FXR nuclear receptors, and naturally occurring anti-inflammatory compounds like boldine or EGCG. Furthermore, systemic pharmacokinetics of drugs and xenobiotics is studied in rats including bioavalability, body distribution, metabolism, biliary and urinary excretions.