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Course, academic year 2024/2025
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Pharmacokinetics - GAF358
Title: Pharmacokinetics
Guaranteed by: Department of Pharmacology and Toxicology (16-16170)
Faculty: Faculty of Pharmacy in Hradec Králové
Actual: from 2023
Semester: summer
Points: 0
E-Credits: 3
Examination process: summer s.:written
Hours per week, examination: summer s.:14/14, C+Ex [HS]
Capacity: unlimited / unlimited (24)
Min. number of students: unlimited
4EU+: no
Virtual mobility / capacity: no
Key competences:  
State of the course: taught
Language: English
Teaching methods: full-time
Level:  
Note: deregister from the exam date if a requisite was not fulfilled
Guarantor: doc. PharmDr. Lukáš Červený, Ph.D.
Comes under: 2.ročník 2024/25 PS povinně volitelné
3.ročník 2024/25 Farmacie
Co-requisite : GAF339, GAF340
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.
Last update: Červený Lukáš, doc. PharmDr., Ph.D. (17.02.2025)
Course completion requirements -

Credit requirements: active participation in two laboratory exercises

The dates of the laboratory sessions are fixed and announced at the beginning of the summer semester. Compared to the schedule in SIS, the laboratory sessions will start earlier, on March 14, 2025. Registration for laboratory sessions is done via a shared Excel sheet (by March 3, 2025). If participation in two out of the three scheduled laboratory sessions is not possible (e.g., due to internships), this must be communicated in advance to allow for an alternative solution. Absence due to illness must be justified with a credible document (a medical report), and the conditions for making up the missed laboratory sessions will be discussed—either through an assessment or, if possible, participation in another session on the same topic.

Lectures: voluntary

Exam: written test

Last update: Červený Lukáš, doc. PharmDr., Ph.D. (17.02.2025)
Literature -

Obligatory:

  • Rang H.P., Ritter J.M., Flower R.J., Henderson G.. Rang&Dale`s Pharmacology. : Elsevier Churchill Livingstone, 2016, s. ISBN 13 978-0-7020-5362-7.

  • Studijní materiály

  • Brunton L.L., Hilal-Dandan R., Knollmann B.C.. Goodman & Gilman's the pharmacological basis of therapeutics. New York: McGraw-Hill, Medical Publishing Division, 2018, 1419 s. ISBN 978-1-25-958473-2.

Last update: prepocet_literatura.php (19.09.2024)
Teaching methods -

lectures and practical laboratory excercises

Last update: Červený Lukáš, doc. PharmDr., Ph.D. (15.02.2024)
Syllabus -

Lectures:

  1. definition/description of principal pharmacokinetic processes, mechanisms of drug permeation across biological barriers and their mathematical description, linear/non-linear pharmacokinetics

  2. role of biotransformation enzymes in pharmacokinetic drug interactions, clinically relevant drug interactions on biotransformation enzymes

  3. 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

  4. role of drug transporters in pharmacokinetic interactions, clinically relevant drug interactions on drug transporters

  5.  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

  6. 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.)

  7. gene polymorphisms and their effect on drug pharmacokinetics, particular gene mutations with proven clinical impact

Laboratory exercises:

  1. monitoring of drug interactions with cytochromes P450, analysis of drug-drug interactions

  2. analysis of drug absorption and the monitoring of interactions on drug transporters (P-glycoprotein, breast cancer resistance protein and more)

  3. monitoring of drug-mediated mRNA induction of selected types of cytochromes in the intestine and hepatic cells

Last update: Červený Lukáš, doc. PharmDr., Ph.D. (17.02.2025)
Learning outcomes -
  • Explains the basic classification and significance of biotransformation enzymes in drug metabolism. Describes the molecular mechanisms underlying drug interactions at the enzymatic level (inhibition and induction). Explains and discusses the impact of the extraction ratio on the outcome of drug interactions and which phase of pharmacokinetics it influences. Describes how the fm parameter contributes to the manifestation of metabolic drug interactions.
  • Lists in vitro models used for studying metabolic drug interactions, describes their principles, advantages, and limitations. Describes the methods and procedures used to test a new drug as a potential substrate, inhibitor, or inducer (including specific isoforms typically tested). Defines general testing schemes, including in silico methods and decision trees used to assess the potential clinical relevance of metabolic interactions (knowledge of decision trees is required only in general terms). Describes the design of in vivo clinical interaction studies and identifies where findings from such studies are published or reported.
  • Explains the role of membrane transporters and their involvement in various pharmacokinetic processes. Lists examples of such transporters and drugs that interact with them. Discusses the possibilities of transporter-mediated drug interactions.

 Based on theoretical knowledge and practical experience, proposes possible methods for studying drug–transporter interactions, including assessment of substrate affinity, inhibition of transporter function, or induction of transporter expression.

  • Discusses factors influencing drug pharmacokinetics, distinguishing between those related to the drug or its formulation, and those related to the organism, including pathological factors and chronopharmacology. For each category, is able to name at least two drugs whose pharmacokinetics are influenced in this manner and explain the nature of the interaction.
  • Explains the fundamental pharmacokinetic processes (ADME) and their relevance to the therapeutic effect of a drug. Discusses the influence of biological barriers and types of transport (passive diffusion, facilitated diffusion, and active transport) on drug absorption, distribution, and elimination. Illustrates the role of transporters (e.g., P-gp, BCRP, OATP, OCT) in these processes using specific examples.
  • Lists and describes the mechanisms of drug transport across biological membranes and explains the application of Fick’s law in passive diffusion. Distinguishes between linear and nonlinear pharmacokinetics and uses Michaelis-Menten kinetics to explain transporter and enzyme saturation.
  • Defines basic in vitro models for studying drug permeability (e.g., Caco-2, MDCK, HEK-293) and describes the principles of bidirectional transport studies. Explains the significance of Papp and efflux ratio parameters for evaluating active transport. Discusses the use of model inhibitors to confirm transport specificity.
  • Explains the molecular basis of pharmacogenetic variations and their impact on drug pharmacokinetics and pharmacodynamics. Describes the most common types of genetic polymorphisms (e.g., SNPs, indels, CNVs) and their effects on the function of enzymes (e.g., CYP2D6, CYP2C9, TPMT) and transporters (e.g., ABCB1, OATP1B1, OCT1).
  • Based on theoretical knowledge and real-world examples, describes how pharmacogenetic differences influence drug efficacy and safety. Provides examples of drugs where patient genotyping is essential for dose optimization (e.g., warfarin, codeine, thiopurines, statins).
Last update: Červený Lukáš, doc. PharmDr., Ph.D. (28.03.2025)
 
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