FA806: Drug Transporters in ADME

The overall aim of the course, is thus that the participants are able to a) experimentally determine kinetic parameters related to transporters b) substantiate the role of drug transporters in overall ADMET properties of a drug compound, including predictions of bioavailability from in-vitro and in-situ experiments using PBPK modeling c) describe the regulatory aspects of transporter interactions of selected drug compounds d) discuss original scientific literature within the field.

The above-mentioned element are important for pharmacist working in the setting of drug discovery and drug development in the pharmaceutical industry as well as for clinical pharmacists and pharmacists working in public administration (e.g. Danish Agency of Medicines or Department of Health or Environment) that relate to the use and approval of drug products.

The course is a continuation of the knowledge, skills and competences acquired in bachelor courses FA502, FA503, FA504, BB524, BMB530, BMB504, and the master course in Drug transport and drug delivery systems.

The course builds on the knowledge, skills and competences acquired in the courses FA502, FA503, FA504, BB524, BMB530, BMB504, and the master course in “Drug transport and drug delivery systems”, and gives an academic basis for performing a Master Thesis project in the area related to ADME drug properties and transporters, that are part of the degree.

In relation to the competence profile of the degree it is the explicit focus of the course to:

• give competences required for participating in project groups working in drug development programs
• give competences required for discussing and approving the use of drug substances and drug products.
• give skills and competences such as for example in vitro-in vivo correlation and PBPK modeling discussing the interaction with drug transporters and the implications for drug delivery, pharmacokinetics and drug-drug interactions
• provide skills in substantiate and calculate the kinetics of drug transporters in barrier tissues and to conduct experiments with in-vitro barrier tissues as well as to interpret experimental flux data
• provide skills in conducting experimental approaches to investigate drug – transporter interaction
• provide competences in analyzing/discussion data involving transporters and transporter kinetics.
• provide skills in sound and critical communication of ADME properties and transporter findings.
• give knowledge about classifying transporters with regard to transporter type, structure, function, and expression in different tissues of the body
• give competences about planning, conducting and evaluating experiments aimed at investigating ADME properties and transport interactions.

• Overall ADMET properties
• Transporter kinetics
• Membrane transporter structure, function and expressiom
• The concepts of flux, permeability and carrier-mediated kinetics
• In vitro and in vivo methods for studying drug transport by membrane transporters the ADME concepts
• Pharmacokinetics and ADME
• Drug uptake and efflux transporters in the small intestine, liver and kidney and their interplay with metabolizing enzymes, drug uptake and efflux transporters in the blood-brain barrier 
  and their role in drug delivery e.g to the CNS.
• PBPK modeling of the role of transporters in drug absorption and pharmacokinetics (Simcyp),
• FDA and EMA guidelines for transporter interactions.
• The e-classes are for calculation and estimation of kinetical parameters that are fundamental for understanding ADME and transporters. Thus students should be able to make basic calculations of e.g. flux and permeability.
• Making report based on exercises, that cover selected aspects of the curriculum:
  In vitro analysis of drug uptake transporter activity, In vitro analysis of drug efflux transporter activity exemplified by studies on the efflux pump P-glycoprotein, calculations of transporter kinetics from in vitro studies, calculations of transporter involvement in oral absorption using computer-based modeling.
  In the exercises, students work in groups of 2-4. Following the exercise, the results are used for preparing a written project report on the subject of the exercise, including background and literature studies. The reports will be performed by the same group that performed the practical exercise. The project reports has to be handed in to-, and approved by a course teacher. The results found must be reported clearly and precisely in keeping with the conventions in force in English-language journals.

• Reading of text book material and scientific paper
• Calculation and presentation of results obtained during the laboratory work
• Evaluation of experimental obtained data
• Preparation of scientific rapport based on the lab work