Syllabus
Lectures: definition/description of principal pharmacokinetic processes, mechanisms of drug permeation across biological barriers and their mathematical description, linear/non-linear pharmacokinetics role of biotransformation enzymes in pharmacokinetic drug interactions, clinically relevant drug interactions on biotransformation enzymes preclinical experimental methods (in vitro, in vivo, in silico models) for quantification of role of biotransformation enzymes in drug pharmacokinetics and monitoring of drug interactions on these enzymes, their advantages/disadvantages, extrapolation of preclinical results to whole human body pharmacokinetics, possibilities of clinical testing role of drug transporters in pharmacokinetic interactions, clinically relevant drug interactions on drug transporters preclinical experimental methods (in vitro, in vivo, in silico models) for quantification of drug transporter role in absorption, distribution and excretion, their pros and cons, extrapolation of preclinical results to whole human body pharmacokinetics, possibilities of clinical testing factors affecting drug pharmacokinetics with special focus on biotransformation enzymes and drug transporters, predictable changes of drug pharmacokinetics in specific types of patients (e.g. in pregnancy, chronic heart failure, impaired function of kidneys etc.) gene polymorphisms and their effect on drug pharmacokinetics, particular gene mutations with proven clinical impact
Laboratory exercises: monitoring of drug interactions with cytochromes P450, analysis of drug-drug interactions analysis of drug absorption and the monitoring of interactions on drug transporters (P-glycoprotein, breast cancer resistance protein and more) monitoring of drug-mediated mRNA induction of selected types of cytochromes in the intestine and hepatic cells
Annotation
Understanding pharmacokinetic mechanisms and the pharmacokinetic drug interactions is crucial for choosing the effective the safe pharmacotherapy. Knowledge on pharmacokinetics and drug interactions is applied in the drug discovery and development and used in the wide range of applied pharmaceutical sciences, mainly in clinical Pharmacology and hospital pharmacy.
In the subject Pharmacokinetics, students will get overview in (i) molecular basis of pharmacokinetic principles and causes of pharmacokinetic drug-drug interaction and Clinical application of this knowledge (ii) actual experimental approaches used in evaluation of pharmacokinetic interactions that are recommended by recognized drug regulatory agencies (FDA and EMA). (iii) Students will get the opportunity to perform these experimental methods by themselves during the practical laboratory excercises.