SFKKIF004U  Drug Transporters in ADME

Volume 2015/2016
Education

Cand.Pharm. - elective, Cand.Scient.Pharm. - elective, MSc in Pharmaceutical Sciences - elective, MSc in Medicinal Chemistry - elective.

Content

The course is based on lectures and lab exercises which revolve around central subjects in the field of drug transporters in ADME. The lectures cover a range of subjects, from individual transporter kinetics, to overall ADME properties drug compounds and the effect of transporter interactions on these.

The following topics will be covered in the lectures;

Membrane transporter structure and function, the concepts of flux and permeability and carrier-mediated transpithelial transport kinetics, in vitro and in vivo methods for studying drug transport by membrane transporters, pharmacokinetics and the ADME concepts, 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 CNS drug delivery,mathematical modeling of the role of transporters in drug pharmacokinetics (Simcyp), FDA and EMEA guidelines for transporter interactions.

The exercises cover selected aspects of the curriculum.

The topics of the exercises will be;

In-vitro analysis of drug uptake transporter activity, exemplified by studies on the intestinal di/tri-peptide transporter hPEPT1, 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 overall pharmacokinetic properties using computer-based modeling.

In the exercises, students work in groups of 5. Following the exercise, the results are used for preparing a written project report on the subject of the exercise, including background and litterature studies. The reports will be performed by the same group which 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.

Discussion classes will be held in the last part of the course, allowing for the students to discuss the contents of the reports with course teachers.

Learning Outcome

Objectives

To introduce students to drug transporting membrane proteins, and their role in determining ADME (Absorption, Distribution, Metabolism, Elimination) properties of drug compounds. Furthermore, the course aims to give an understanding of how these interactions may be addressed in the design of drug delivery systems, as well as the regulatory implications of transporter interactions. Finally, the course aims to introduce and train the students in the use of IT tools for evaluating drug absorption and transporter interactions.

 

Course outcome

At the end of the course, students are able to:

Knowledge

  • Understand the regulatory aspects of transporter interactions of selected drug compounds

 

Skills

  • Perform a critical evaluation of original scientific literature within the field
  • Understand the role of drug transporters in overall ADME properties of a drug compound, including predictions of bioavailability from in-vitro and in-situ experiments using computer-based modeling.

 

Competences

  • Understand 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.

Textbooks

Steffansen, B, Brodin, B & Nielsen, C.U.: Molecular Biopharmaceutics. 1 ed. ULLA pharmacy series, Pharmaceutcial Press 2010.

Sugiyama, Y. & Steffansen, B.: Transporters in drug development. 1 ed. AAPSpress, Springer 2013

Rowland, M. & Tozer, T.N.: Clinical Pharmacokinetics and Pharmacodynamics. Concepts and Applications, 4th ed., Lippincott, Williams & Wilkins, 2011

Original research papers and reviews available from the course website.

FDA/EMEA guidelines on transporter interactions

Laboratory exercise manual

Prerequisites;
Course teaching is based on the assumption that students have a Bachelor's degree as a minimum, and has followed and completed courses covering basic pharmacology, organic chemistry and physical chemistry (see also academic qualifications).
Lectures
Laboratory exercises in groups of 5
Project reports in groups of 5
Classroom discussions
Credit
7,5 ECTS
Type of assessment
Oral examination, 20 min
Examination design
At the end of the course each student takes an oral exam (20 min), which consists of a 10 minute examination in a randomly chosen subject from the curriculum and a 10 min discussion of the contents of one of the exercise reports. The two parts of the examination will contribute equally to the final grade.
Exam registration requirements

Satisfactory participation in all laboratory work and discussion classes, satisfactory effort in connection with designing laboratory exercise reports.

Submitting five written project reports on the basis of practical exercises. The reports will be performed by the same group which performed the practical exercise. The project reports has to be handed in to - and approved by - a course teacher.

Aid
Written aids allowed
Marking scale
7-point grading scale
Censorship form
No external censorship
Criteria for exam assesment

To achieve the grade 12 the student must

Knowledge

  • Understand the regulatory aspects of transporter interactions of selected drug compounds
  • Command of explaining general kinetic, structural and physiological aspects of membrane transporting drug transporters

 

Skills

  • Perform a critical evaluation of original scientific literature within the field
  • Understand the role of drug transporters in overall ADME properties of a drug compound, including predictions of bioavailability from in-vitro and in-situ experiments using computer-based modeling.

 

Competences

  • Understand 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
  • Category
  • Hours
  • Lectures
  • 20
  • Practical exercises
  • 25
  • Project work
  • 75
  • Colloquia
  • 10
  • Course Preparation
  • 56
  • Exam
  • 20
  • Total
  • 206