Module 2: Pharmaco-Toxicokinetics

Date of release/last update: created 13-03-2016, last version 19-10-2017


  • Fernando Remião (UPorto)
  • Ana Rita Lima (UPorto)
  • Daniela Rodrigues (U.Porto)
  • Renata Silva (U.Porto)
  • Carolina Rocha-Pereira (U.Porto)
  • Ricardo Dinis-Oliveira (U.Porto)
  • Helena Carmo (UPorto)
  • Félix Carvalho (UPorto)
  • Maria de Lourdes Bastos (UPorto)

Short descriptions

This module aim to describe the phenomena of pharmaco-toxicokinetic and contextualize the pharmacological and toxicological consequences related to the absorption, distribution, metabolism, excretion and transport (ADMET) of xenobiotics (drugs and toxic compounds). The students will contact with movies showing the ADMET processes as well as research data that will allow them to interpret the risks associated with xenobiotic exposure related to their disposition in the organism.

Intended learning outcomes        

The main Learning Objectives of this module are:

  • To understand the main ADMET related processes, namely the mechanism by which the xenobiotics pass through the membranes, as well as the main pathways and barriers concerning absorption, distribution and excretion of xenobiotics;
  • To know the main metabolic processes, highlighting the classic mechanisms of bioactivation;
  • To recognize important ADMET phenomena related to the variability of biological and genetic aspects, which modulate pharma and toxicological effects of xenobiotics.

Learning Outcomes: at the end of this module, the learner should be able to:

  • Concerning mechanism by which xenobiotics pass through membranes:
    • Differentiate the known transport mechanisms;
    • Describe the main chemical characteristics of xenobiotics that are favorable to their pass through membranes;
    • Predict the transport mechanism, considering the physical-chemical characteristics of the xenobiotics;
    • Relate the membrane transporters with phase 0 and 3 in cellular influx and efflux of xenobiotics;
    • Interpret the biological consequences of xenobiotics interactions at transport level
  • Concerning main pathways and barriers related to absorption, distribution and excretion of xenobiotics:
    • Explain the main pathways by which xenobiotics are absorbed, highlighting the gastrointestinal, pulmonary and dermic routes;
    • Predict the xenobiotic bioavailability and distribution, considering the route of exposure;
    • Describe the main factors that modulate the distribution of xenobiotics (protein-binding, tissue accumulation and organ protected barriers, as blood-brain-barrier and placenta);
    • Compare the xenobiotics distribution in relation with their physical-chemical characteristics;
    • Describe the main routes and mechanisms of xenobiotic elimination
    • Interpret the xenobiotic interactions at excretion mechanisms
    • Predict xenobiotic mechanism of excretion, considering its physical-chemical characteristics
  • Concerning the xenobiotic metabolism:
    • Identify the main metabolic organs;
    • Describe the different metabolic phases (Phase 1 and 2)
    • Interpret the way by which Phase 0 and 3 modulate the metabolic processes
    • Explain the phase I metabolism, namely the microsomal and the non-microssomal enzymatic reactions, as well as types of reactions (oxidation, reduction, hydrolysis) and the main enzymes catalyzing these reaction;
    • Illustrate the importance of Cytochrome P450 in xenobiotic metabolism, highlighting the principal isoenzymes involved;
    • Explain the phase II metabolism;
    • Recognize the main bioactivation processes, namely reactions (e.g. oxidation, reduction, glucuronidation); enzymes involved (e.g. Cytochrome P450, Peroxidases and Glucuronosyl transferases); chemical structures (e.g. epoxides, quinones, aromatic amines);
    • Discriminate the detoxification/bioactivation pathways in metabolic profile of classic xenobiotics in Toxicology.
  • Concerning ADMET processes variability phenomena:
    • Relate the biological and genetic variability in ADMET processes with pharma and toxicological outcomes of xenobiotics.

Module structures (Topics)          

2.1 ADMET, Membrane and Transport Mechanisms (1 ECTS)

  • Main concepts: Absorption, distribution, metabolism, excretion and transport (ADMET)
  • Chemical and Physical Membrane characteristics
  • Xenobiotic transport mechanisms
  • Passive transport
  • Active transport
  • Phase 0 and 3 in cellular influx and efflux of xenobiotics
  • Xenobiotic interactions at transport level
  • Biological and genetic variability in ADMET

2.2 ABC Transporters, BBB Barrier (2 ECTS)

  • ADMET and Membrane Transporters
  • Transporters at Blood-Brain-Barrier (BBB) and other tissues
  • Xenobiotic interactions at transport level, Transporters variability and biological consequences

 2.3 Absorption, Distribution, Excretion of xenobiotics (2 ECTS)

  • Toxicokinetics and main routes of xenobiotics absorption, distribution and excretion
  • Factors that modulate the distribution of xenobiotics (protein-binding, tissue accumulation)
  • Main barriers concerning distribution (Blood-Brain-barrier and Placenta)

2.4 Xenobiotic Metabolism (2 ECTS)

Phase 1 reactions

  • Oxidations, reductions and hydrolysis
  • Microsomal reactions (Cytochrome P450)
  • Non-microsomal reactions (Alcohol and Aldehyde dehydrogenase, Epoxide Hydrolase and Esterases)

Phase 2 reactions

  • Glucuronidation, sulfonation, acetylation, methylation and conjugation with glutathione, amino-acids and CoA
  • Detoxification/bioactivation pathways (e.g. paracetamol, salicylates, benzo(a)pyrene, aflatoxin B1)

Estimated workload        

6 ECTS: 168 hours


Students (University, PhD or Master) of degrees:

  • Pharmacy
  • Medicine
  • Nursing
  • Veterinary medicine
  • Biology
  • Environmental Engineering
  • Forensic sciences

Students of Vocational training:

  • Pharmacy assistant
  • Nursing assistant
  • Veterinary assistant
  • Laboratory technicians
 Professionals in fields related to toxicology:
  • Pharmacists
  • Occupational medicine professionals
  • Forensics
  • Supervisory bodies
  • Police forces 

General audience interested in toxicology

Available languages          

English, Spanish, Portuguese, Italian, Czech, Romanian, Bulgarian, Finnish

First, an English or native language version of each author will be created. Translations into the languages of all involved countries and English will be the final outcome.