Pharmacokinetics and Pharmacodynamics

Cellular and molecular biology, Biochemistry, Organic Chemistry, Anatomy and Physiology

The syllabus consolidates the fundamental principles of Pharmacokinetics and Pharmacodynamics (PK/PD), promoting their application to the resolution of practical cases and real-world scenarios, with the aim of developing analytical thinking, critical reasoning and decision-making skills. The proposed learning activities also emphasise the integrated application of knowledge in increasingly complex contexts, fostering the acquisition of both theoretical and practical PK/PD competencies.

The selected teaching methods (TM) combine a range of innovative pedagogical strategies based on active, student-centred learning, promoting the integrated development of the three dimensions of learning: knowledge (knowing), skills (knowing how to do) and competences (knowing how to be).

TM1 – Interactive lectures: delivery of theoretical content using appropriate audiovisual resources, complemented by individual active learning activities focused on solving PK/PD problems to consolidate and apply knowledge, using the Mentimeter platform (Word Cloud, Q&A, Multiple Choice and Ranking).

TM2 – Collaborative learning: interactive lectures complemented by group-based activities centred on the critical appraisal and discussion of PK/PD scientific papers, using the Jigsaw methodology to promote cooperative learning and knowledge integration.

TM3 – Practice-based learning: development of technical competencies through the analysis and resolution of PK/PD practical cases in an applied context, emphasising practical execution, interpretation of results and evidence-based decision-making.

TM4 – Problem-Based Learning (PBL): analysis and resolution of PK/PD practical cases using online software and digital tools, encouraging clinical reasoning, autonomous learning and problem-solving skills.

TM5 – Project-based learning: development of competencies through the design of scientific and technical protocols in the field of bioavailability and bioequivalence (BA/BE), promoting the integration of acquired knowledge and the application of current regulatory guidelines.

TM6 – Planning- and problem-solving-based learning: development of competencies in the analysis and resolution of PK/PD practical cases in accordance with current regulatory guidelines. The integration of the theoretical principles of pharmacokinetics and pharmacodynamics with a structured programme of progressively more complex problem-solving activities facilitates both horizontal and vertical integration with related course units, namely Pharmacology I, Pharmacology II, Pharmacotherapy I and Pharmacotherapy II.

THEORETICAL COMPONENT

C1. Understand the processes of drug absorption, distribution, metabolism and excretion, as well as the factors that influence them.

C2. Identify the main pharmacological targets and understand the general mechanisms of drug action, relating them to the pharmacological response.

C3. Identify, interpret and predict pharmacokinetic and pharmacodynamic drug interactions and evaluate their impact on the efficacy and safety of pharmacotherapy.

C4. Identify the main factors responsible for variability in drug response, including physiological, pathological, genetic and therapeutic factors.

C5. Integrate pharmacokinetic and pharmacodynamic knowledge to solve clinical and experimental problems, applying critical, systems and collaborative thinking approaches to support evidence-based decision-making.

PRACTICAL COMPONENT

C6. Understand the time course of plasma drug concentrations according to the pharmaceutical dosage form and the route of administration.

C7. Calculate and interpret the main pharmacokinetic parameters using both compartmental and non-compartmental pharmacokinetic analysis methods.

C8. Understand and apply the principles and regulatory requirements governing bioequivalence studies of medicinal products.

THEORETICAL COMPONENT

Module 1. PHARMACOKINETICS

1.1. Delivery of active substances into the body following different routes of administration and dosage forms

1.1.1. Routes of administration and dosage forms

1.1.2. Oral drug administration

1.2. ADME: Absorption

1.2.1. Drug absorption following oral administration

1.2.2. Sites of absorption of orally administered drugs

1.2.3. Mechanisms of active substance transport across cell membranes

1.2.4. First-pass effect and pre-systemic degradation of active substances

1.2.5. Factors affecting the oral absorption of active substances

1.2.6. Pharmacokinetic absorption parameters: absorption rate constant, maximum concentration, time to maximum concentration and bioavailability

1.3. Bioavailability

1.3.1. Definition of bioavailability

1.3.2. Factors affecting bioavailability

1.3.3. Absolute bioavailability

1.3.4. Relative bioavailability

1.3.5. Methodologies for the determination of bioavailability

1.3.6. Bioequivalence

1.4. Biopharmaceutics Classification System

1.4.1. The Biopharmaceutics Classification System: solubility and permeability

1.4.2. Classification of active substances: Classes I, II, III and IV

1.4.3. Waivers of in vivo studies (Biowaivers)

1.4.4. Biopharmaceutics Drug Disposition Classification System (BDDCS)

1.5. ADME: Distribution

1.5.1. Distribution within the vascular compartment

1.5.1.1. Plasma protein binding: albumin and alpha-1-acid glycoprotein

1.5.1.2. Free and bound drug fractions

1.5.1.3. Factors affecting plasma protein binding

1.5.2. Distribution within the extravascular compartment

1.5.2.1. Factors affecting tissue distribution: drug binding to plasma and tissue proteins, rate of drug delivery to tissues, and permeability across biological membranes

1.5.2.2. Tissue accumulation of drugs

1.5.3. Physiological barriers to drug distribution

1.5.3.1. Blood-brain barrier

1.5.3.2. Blood-testis barrier

1.5.3.3. Placental barrier

1.5.4. Pharmacokinetic distribution parameter: apparent volume of distribution

1.6. ADME: Metabolism

1.6.1. Biotransformation: active drugs, prodrugs and metabolites

1.6.2. Biotransformation reactions: Phase I and Phase II

1.6.3. Enzyme systems involved in drug biotransformation

1.6.3.1. Cytochrome P450 multiplicity and isoenzymes

1.6.4. Factors affecting drug biotransformation

1.6.5. Paracetamol biotransformation

1.6.6. Hepatic extraction ratio

1.6.7. Metabolic kinetics

1.7. ADME: Excretion

1.7.1. Routes of drug excretion: organs and body fluids involved

1.7.2. Renal excretion

1.7.3. Biliary excretion and the enterohepatic circulation

1.7.4. Excretion into breast milk

1.8. Elimination kinetics

1.8.1. Concepts of drug input, disposition and elimination

1.8.2. Zero-order and first-order elimination kinetics

1.8.3. Pharmacokinetic elimination parameters: elimination rate constant, elimination half-life and clearance

1.8.4. Steady state

Module 2. PHARMACODYNAMICS

2.1. General mechanisms of drug action

2.1.1. Pharmacological target, mechanism of action and pharmacological response

2.1.2. Main pharmacological targets and mechanisms of drug action

2.1.2.1. Receptors: agonists and antagonists

2.1.2.2. Enzymes: inhibitors, false substrates, prodrugs and cofactors

2.1.2.3. Ion channels: blockers and allosteric modulators

2.1.2.4. Transporters: inhibitors and false substrates

2.1.3. Pharmacological response: therapeutic effects, adverse effects, placebo effect and nocebo effect

2.1.4. Pharmacokinetic/pharmacodynamic (PK/PD) relationship

2.1.5. Dose-response curve: Emax and ED50/EC50

2.2. Pharmacological receptors

2.2.1. Ionotropic receptors

2.2.2. Metabotropic receptors

2.2.3. Receptors with intrinsic kinase activity or kinase-associated receptors

2.2.4. Nuclear receptors

2.2.5. Post-translational modifications of receptors and macromolecular complexes

2.2.6. Alpha- and beta-adrenergic, muscarinic, nicotinic, GABAergic, dopaminergic, serotonergic and histaminergic receptors

2.3. Drug-receptor interactions

2.3.1. Definitions of selectivity, affinity, intrinsic efficacy and potency

2.3.2. Dose-response curves (full agonists, partial agonists, inverse agonists and antagonists)

2.3.3. Desensitisation, tolerance and resistance

2.3.4. Types of concentration-effect relationships: indirect effects, irreversible effects and reversible direct effects

2.3.5. Application of receptor theory and the Hill equation

Module 3. VARIABILITY IN PHARMACOLOGICAL RESPONSE

3.1. Concept of variability: inter-individual and intra-individual variability

3.2. Clinical impact of pharmacokinetic and pharmacodynamic variability

3.3. Drug interactions

3.3.1. Pharmacokinetic interactions

3.3.1.1. Absorption

3.3.1.2. Distribution: displacement from plasma protein binding

3.3.1.3. Metabolism: enzyme inhibition and induction

3.3.1.4. Excretion

3.3.2. Pharmacodynamic interactions

3.4. Other sources of variability

3.4.1. Sex differences

3.4.2. Extremes of age (paediatric and geriatric populations)

3.4.3. Comorbidities: renal disease

3.4.4. Genetic differences (pharmacogenetics)

3.4.5. Circadian rhythm (chronopharmacokinetics)

3.4.6. Pregnancy

PRACTICAL COMPONENT

Module 1. NON-COMPARTMENTAL PHARMACOKINETIC ANALYSIS

1.1. Calculation of pharmacokinetic parameters

1.1.1. Maximum concentration (Cmax) and time to maximum concentration (tmax)

1.1.2. Terminal elimination rate constant (λz)

1.1.3. Elimination half-life (t½)

1.1.4. Area under the concentration-time curve (AUC₀-t) using the trapezoidal rule

1.1.5. Area under the concentration-time curve extrapolated to infinity (AUC₀-∞)

1.1.6. Apparent volume of distribution (Vz/F)

1.1.7. Oral clearance (CL/F)

Module 2. PHARMACOKINETIC CLINICAL STUDIES

2.1. Phases of drug development

2.2. Pharmacokinetic clinical studies: study design, investigational medicinal product and administration conditions, participants, sampling strategy, collection and determination of drug and/or metabolite concentrations in biological samples, pharmacokinetic analysis and statistical analysis

Module 3. GUIDELINES FOR THE INVESTIGATION OF BIOEQUIVALENCE

3.1. Development and approval of new medicinal products

3.2. Originator and generic medicinal products

3.3. Equivalence between medicinal products

3.4. European Medicines Agency (EMA) guidelines on bioequivalence studies

3.4.1. Reference product and test product

3.4.2. Study design

3.4.3. Participants

3.4.4. Standardisation and experimental conditions

3.4.5. Sampling

3.4.6. Bioanalytical methodology

3.4.7. Pharmacokinetic analysis

3.4.8. Parameters analysed and acceptance criteria

3.4.9. Statistical analysis of results

Module 4. COMPARTMENTAL PHARMACOKINETIC ANALYSIS

4.1. Compartmental pharmacokinetic models: one-, two- and three-compartment models

4.1.1. One-compartment model

4.1.1.1. Equations describing concentration-time profiles following intravenous bolus administration, intravenous infusion and extravascular (oral) administration

4.1.1.2. Single-dose and multiple-dose administration

4.1.1.3. Calculation of pharmacokinetic parameters: maximum concentration (Cmax), time to maximum concentration (tmax), elimination rate constant (ke), elimination half-life (t½), apparent volume of distribution (Vd), clearance (CL) and area under the concentration-time curve (AUC)

Module 5. DOSE-RESPONSE CURVE ANALYSIS

5.1. Construction of dose-response and concentration-effect curves

5.1.1. Parameters: Emax, ED50, EC50 and Hill coefficient

5.1.2. Models of agonism and antagonism

1. Continuous Assessment

Theoretical Component (15 marks)

The theoretical component is assessed through two written tests held during the teaching period. Students must obtain a minimum mark of 9.5 out of 20 in each written test. The final mark for the theoretical component is the arithmetic mean of the marks obtained in the two written tests.

Practical Component (5 marks)

The practical component is assessed on a continuous basis through students' participation and performance in the practical class activities. To pass this component, students must obtain a minimum mark of 9.5 out of 20.

The final mark for the course unit is calculated as the weighted average of the Theoretical Component (75% - 15 marks) and the Practical Component (25% - 5 marks).

2. Examination

During the Regular, Supplementary and Special Examination periods, assessment is carried out through a written examination covering both the theoretical and practical components of the course unit.

The final mark is calculated as the weighted average of the Theoretical Component (75% - 15 marks) and the Practical Component (25% - 5 marks). Students must obtain a final mark of at least 9.5 out of 20 to pass the course unit.

Assessment is conducted in accordance with the Academic Regulations currently in force.

NAO