ADME

Course Objective

“What happens to a drug inside the human body?”

This course will dive into the biochemical processes underlying the absorption (A), distribution (D), metabolism (M) and excretion (E) of drugs (or xenobiotics, in general): the ADME processes, an essential discipline in pharmaceutical sciences.

Course Content

Of the thousands of novel compounds that are developed in drug discovery programs, only a fraction has the appropriate pharmacokinetic properties to become a drug product. Pharmacokinetics is determined by the complex processes involved in absorption (A), distribution (D), metabolism (M) and excretion (E) of the drug in the human body, the so-called ADME processes. ADME processes directly impact drug effectiveness (pharmacodynamics), safety and dosage. ADME processes do not only apply to pharmaceutical drugs, but environmental contaminants, nutraceuticals or phytochemicals may follow analogous processes. In this course, the student will learn: the fundamentals of ADME, state-of-the-art analytical chemistry approaches to study ADME, and inter-individual variability impacting ADME.

In this course, the students will be familiarised with:

Drug Absorption

• routes of administration, with emphasis on the gastro-intestinal tract (GIT);
• drug transporters involved in absorption;
• how much drug reaches systemic circulation

Drug Distribution

• how does the drug spread through the body’s tissues and fluids;
• blood brain barrier;
• drug protein binding and volume of distribution

Drug Metabolism

• how does the body chemically change the drug;
• xenobiotic metabolism mostly in the liver and gut, mediated by major enzymes classes and isoforms: CYPs, UGTs, SULTs, etc, and integrated metabolic pathway maps;
• (re)active metabolites and drug-drug interactions

Drug Excretion

• how does the body eliminate the drug (often via urine or bile);
• drug transporters involved in excretion;
• drug clearance and entero-hepatic recirculation

Methods and approaches to study ADME processes

• biochemical, cellular, pre-clinical and clinical studies;
• analytical chemistry tools to monitor drugs and metabolites thereof in biological samples: LC-MS and NMR metabolomics;
• strategies to perform drug metabolite identification (metID) from LC-MS/MS;
• bioanalytical strategies for bio-affinity profiling of metabolic mixtures;
• use of (stable) isotopically labelled drugs to study ADME

Factors impacting ADME processes

• physico-chemical properties of drugs;
• inter-individual variability in: environmental factors, genetic variants (metabolic enzymes, transporters), sub-populations;
• personalised medicine

Additional Information Teaching Methods

Lectures and assignments

Method of Assessment

Written exam and assignments

Literature

Consulting books:

1. ‘ADME Processes in Pharmaceutical Sciences’. Eds. Alan Talevi, Pablo A. M. Quiroga. Springer 2018, ISBN 978- 3-319-99593-9 2.
2. 'Rang & Dale's Pharmacology’. Eds. J.M. Ritter and R.J. Flower. Elsevier 2023, ISBN: 978-0-3238-7395-6.
3. ‘Drug-like properties: concepts, structure design and methods. From ADME to Toxicity optimization.’ Eds. E.H. Kerns and L. Di, Academic Press, 2008, ISBN: 978-0-1236-9520-8.

Additional course material will be provided in Canvas.

Additional Information Target Audience

All MSc DDS specialisations, MSc Biomolecular Sciences, and MSc Chemistry (tracks Chemistry of Life, Molecular Sciences, and Analytical Sciences)

Recommended background knowledge

Background knowledge in chemistry is recommended.